Culture

Oncotarget published "Transcriptome analyses of urine RNA reveal tumor markers for human bladder cancer: validated amplicons for RT-qPCR-based detection" which reported that in case of bladder cancer, urine RNA represents an early potentially useful diagnostic marker.

Here the authors describe a systematic deep transcriptome analysis of representative pools of urine RNA collected from healthy donors versus bladder cancer patients according to established SOPs.

This analysis revealed RNA marker candidates reflecting coding sequences, non-coding sequences, and circular RNAs.

Next, they designed and validated PCR amplicons for a set of novel marker candidates and tested them in human bladder cancer cell lines.

This Oncotarget work strongly suggests exploiting urine RNAs as diagnostic markers of bladder cancer and it suggests specific novel markers.

This Oncotarget work strongly suggests exploiting urine RNAs as diagnostic markers of bladder cancer and it suggests specific novel markers.

Dr. Georg Sczakiel from The Universität zu Lübeck and UKSH, said "Human bladder cancer (BCa) is one of the most common cancer types in humans."

With regard to BCa, RNA markers have been studied by transcriptome analyses of single cells, tissue samples and urine.

In case of BCa, urine is thought to be the most promising source for RNA-based tumor markers as direct physical contact between tumor cells and urine seems to be given.

On the other hand, urine RNA samples contain RNAs which are suitable for cDNA synthesis and RT-qPCR detection.

Cell-free RNA contained in urine samples can be protected against degradation, i.e., stabilization of RNA markers is possible such that shipping of samples and storage is possible.

This consists of SOP-based acquisition of urine, stabilization of urine RNA, delivery and storage of samples, RNA preparation, and deep transcriptome analyses.

The Sczakiel Research Team concluded in their Oncotarget Research Output that while all of these hits focus on conventional linear transcripts the authors also noted experimental evidence supporting the existence of circular RNAs that seem to be able to monitor differences between the healthy state and the cancer state.

This is reflected by a number of recent studies describing a link between circular RNA and cancer.

However, such evidence derived from in silico analyses does not necessarily prove that such circRNAs exist in reality.

A set of experimental evidence is necessary to sufficiently strongly verify their existence.

However, such assays go beyond the scope of this study although this is one promising way to proceed in order to identify new and potent RNA markers.

A new study by Thomas Le Barbanchon and Julien Sauvagnat, two Associate Professors at Bocconi University, published in the Journal of the European Economic Association, finds that electoral districts with a larger gender pay gaps show favoritism toward male political candidates in Parliamentary elections, with fewer female candidates on the ballot.

Professors Le Barbanchon and Sauvagnat gathered data for seven parliamentary elections in France between 1988 and 2017. They studied candidates from the Left and Right political coalitions, which account for 80% of elected members of Parliament. The researchers consulted administrative and web data on candidates and electoral outcomes, survey data on voters' attitude towards gender, as well as census data on earnings, and voters' demographics across electoral districts.

Analysis found that female candidates made up approximately 15% of all Parliamentary candidates in the 1980s and 1990s. The figure doubled to nearly 30% following the implementation of the Parity Law in 2000, which stipulated that each party should have an equal fraction of male and female candidates across electoral districts in Parliamentary elections. Noncompliance with the parity rule results in a financial penalty to the public funding provided to political parties.

Researchers analyzed local gender pay gaps compared to voting support for male and female candidates in the same electoral districts. "We found a positive and strong correlation between gender earnings gaps and electoral gaps across municipalities of the same electoral district: a €150 increase in gender monthly earnings gap leads to an increase by 0.6 percentage points in vote share gap between male and female candidates," Professor Le Barbanchon said.

"Female candidates obtain lower votes in areas with less favorable attitudes towards women, including significant gender pay gaps, and thus women are less likely to run for elections in these areas," Professor Sauvagnat said.

Indeed, researchers found that voters' attitudes towards gender are strongly associated with the gender distribution of candidates across electoral districts within France. A 10 percentage points increase in survey respondents who thought that men were better political leaders than women correlated with a 2.3 percentage points decrease in the share of female candidates.

Researchers concluded that in districts with strongest electoral competition, the electoral cost of selecting women outweighs the cost of the financial penalty under the Parity Law. When voters are biased against female candidates, electoral competition limits the effectiveness of "soft" quota rules on candidates. In the last Parliamentary election (17 years after the Parity rule was introduced) the two main political parties still selected an average of 40% of female candidates, significantly below the 50% objective of the Parity Law.

"Overall, we find that parties allocate female candidates across districts strategically," the authors concluded. "This is very clear after the introduction of the Parity Law. Then parties avoid putting women on the ballot of the most contested districts. In such districts, voters biased against female politicians may lead women to lose the few votes that matter for winning the close race, and parties internalize this competitive disadvantage."

Researchers at the University of Freiburg and the University of Stuttgart have developed a new process for producing movable, self-adjusting materials systems with standard 3D-printers. These systems can undergo complex shape changes, contracting and expanding under the influence of moisture in a pre-programmed manner. The scientists modeled their development based on the movement mechanisms of the climbing plant known as the air potato (Dioscorea bulbifera). With their new method, the team has produced its first prototype: a forearm brace that adapts to the wearer and which can be further developed for medical applications. This process has been collaboratively developed by Tiffany Cheng and Prof. Dr. Achim Menges from the Institute of Computational Design and Construction (ICD) and the Integrative Computational Design and Construction for Architecture Cluster of Excellence (IntCDC) at the University of Stuttgart, together with Prof. Dr. Thomas Speck from the Plant Biomechanics Group and the Living, Adaptive and Energy-autonomous Materials Systems Cluster of Excellence (livMatS) at the University of Freiburg. The researchers are presenting their results in the journal Advanced Science.

4D-printing defines shape changes

3D-printing has established itself as a manufacturing process for a wide range of applications. It can even be used to produce intelligent materials and material systems that remain in motion after printing, autonomously changing shape from external stimuli such as light, temperature or moisture. This so-called '4D-printing', in which predetermined shape changes can be triggered by a stimulus, immensely expands the potential applications of material systems. These changes in shape are made possible by the chemical composition of the materials, which consist of stimuli-responsive polymers. However, the printers and base materials used to produce such materials systems are usually highly specialized, custom-made and expensive - until now.

Now, using standard 3D-printers, it is possible to produce materials systems that react to changes in moisture. Given their structure, these materials systems can undergo shape changes in the entire system or simply in the individual parts. The researchers at the Universities of Freiburg and Stuttgart combined multiple swelling and stabilizing layers to realize a complex movement mechanism: a coiling structure that pulls tighter by unfolding 'pockets' as pressors and which can loosen up again on its own when the 'pockets' release and the coiled structure returns to the open state.

Natural movement mechanisms transferred to technical material systems

For this new process, the scientists used a mechanism from nature: the air potato climbs trees by applying pressure to the trunk of the host plant. To do this, the plant first winds loosely around a tree trunk. Then it sprouts 'stipules', basal outgrowths of the leaves, which increase the space between the winding stem and the host plant. This creates tension in the winding stem of the air potato. To imitate these mechanisms, the researchers constructed a modular material system by structuring its layers so that it can bend in different directions and to different degrees, thereby coiling and forming a helix structure. 'Pockets' on the surface cause the helix to be pushed outwards and put under tension, causing the entire material system to contract.

"So far, our process is still limited to existing base materials that respond to moisture," says Achim Menges. "We're hoping," Thomas Speck adds, "that in the future, inexpensive materials that also respond to other stimuli will become available for 3D-printing and can be used with our process."

Living, Adaptive and Energy-autonomous Materials Systems Cluster of Excellence (livMatS)

Researchers at the University of Freiburg's Living, Adaptive and Energy-autonomous Materials Systems Cluster of Excellence (livMatS) are developing life-like materials systems that are inspired by nature. Like living structures they adapt autonomously to different environmental factors, generate clean energy from their environment and are impervious to damage or can heal themselves. Nevertheless these materials systems will be purely technical objects, so they can be produced using synthetic methods and deployed in extreme conditions. Thomas Speck is a member of the team of speakers at the Cluster of Excellence.

Nashville, Tenn. (4:14 p.m. EDT--July 9, 2021)--Orthopedic surgeons know that knee surgeries that require revisions have inferior outcomes compared with primary surgeries but until now, the reason for this was unknown. Today a team of orthopedic physicians reports that opting for a transtibial surgical approach and choosing an inference screw for femoral and tibial fixation will improve the patient's odds of having a significantly better six-year clinical outcome.

The research was presented today at the American Orthopedic Society of Sports Medicine- Arthroscopy Association of North America Combined 2021 Annual Meeting by Rick Wright MD, Vanderbilt University Medical Center, Nashville, TN.

A team of orthopedic physicians and researchers from Washington University, St. Louis, MO., and Vanderbilt University Medical Center in Nashville, Tenn., designed a study to determine if surgical factors performed at the time of revision anterior cruciate ligament reconstruction have the ability to influence a patient's outcome at six-year follow-up.

Anterior cruciate ligament injury, which usually comprises a complete rupture or tear of the ligament, is one of the most common knee injuries. Surgery comprises ACL reconstruction, where the damaged ACL is replaced by either an autograft (tissue, such as part of the patellar tendon or hamstring tendons, extracted from the person's own body) or an allograft (a specially treated tendon or ligament extracted from a human cadaver) under arthroscopic control.

The researchers enrolled 1,234 revision ACL reconstruction patients (58 % male and 42 % female) between 2006 and 2011. Data collected included baseline demographics, surgical technique and pathology, and a series of validated patient-reported outcome instruments (IKDC, KOOS, WOMAC, and Marx activity rating score). Patients were followed up for 6 years and asked to complete the identical set of outcome instruments.

At six years, follow-up was obtained on 77% (949/1234) of the patients. The researchers found three significant drivers of poor outcomes among these patients, including that surgical variables driving outcome in revision patients were related to femoral and tibial fixation.

Using an interference screw for femoral fixation compared with a cross-pin resulted in significantly better outcomes in six-year IKDC scores (OR=2.2; 95% CI=1.2, 3.8; p=0.008), KOOS sports/rec and KOOS QOL subscales (OR range = 2.2-2.7; 95% CI=1.2, 3.8; p

Using an interference screw for tibial fixation compared to any combination of tibial fixation techniques also resulted in significantly improved IKDC (OR=2.0; 95% CI=1.3, 2.9; p=0.001), KOOS pain, ADL, sports/rec (OR range=1.5-1.6; 95% CI=1.0, 2.4; p

Using a transtibial surgical approach compared to an anteromedial portal approach resulted in significantly improved KOOS pain and QOL subscales at six years (OR=1.5; 95% CI=1.02, 2.2; p

Regarding tunnel position at the time of the revision surgery, surgeons who noted that the tibial tunnel aperture position was in the 'optimum position' fared significantly worse in six-year IKDC scores (OR=0.6; 95% CI=0.4, 0.8; p=0.003), Marx activity levels (OR=0.20; 95% CI=0.07, 0.6; p=0.005), KOOS symptoms, pain, sports/rec, and QOL subscales (OR range=0.56-0.68; 95% CI=0.38, 0.47; p

The research team also noted other factors that affected outcomes, including: lower baseline outcome scores, lower baseline activity level, being a smoker at the time of the revision, higher BMI, female gender, shorter time since the patient's last ACL reconstruction, and having a previous ACL reconstruction on the contralateral side all significantly increased the odds of reporting poorer clinical outcomes at 6 years.

"There are surgical variables that the physician can control at the time of an ACL revision which have the ability to modify clinical outcomes," said Dr. Rick Wright, "Based on outcomes at 6 years, opting for a transtibial surgical approach and choosing an inference screw for femoral and tibial fixation, will improve the patient's odds of having a significantly better 6-year clinical outcome."

Plants have microscopically small pores on the surface of their leaves, the stomata. With their help, they regulate the influx of carbon dioxide for photosynthesis. They also use the stomata to prevent the loss of too much water and withering away during drought.

The stomatal pores are surrounded by two guard cells. If the internal pressure of these cells drops, they slacken and close the pore. If the pressure rises, the cells move apart and the pore widens.

The stomatal movements are thus regulated by the guard cells. Signalling pathways in these cells are so complex that it is difficult for humans to intervene with them directly. However, researchers of the Julius-Maximilians-Universität (JMU) Würzburg in Bavaria, Germany, nevertheless found a way to control the movements of stomata remotely - using light pulses.

Light-sensitive protein from algae used

The researchers succeeded in doing this by introducing a light-sensitive switch into the guard cells of tobacco plants. This technology was adopted from optogenetics. It has been successfully exploited in animal cells, but the application in plant cells it is still in its infancy.

The team led by JMU biophysicist and guard cell expert Professor Rainer Hedrich describes their approach in the prestigious scientific journal Science Advances. JMU researchers Shouguang Huang (first author), Kai Konrad and Rob Roelfsema were significantly involved.

The group used a light-sensitive protein from the alga Guillardia theta as a light switch, namely the anion channel ACR1 from the group of channelrhodopsins. In response to light pulses, the switch ensures that chloride flows out of the guard cells and potassium follows. The guard cells lose internal pressure, slacken and the pore closes within 15 minutes. "The light pulse is like a remote control for the movement of the stomata," says Hedrich.

Anion channel hypothesis confirmed

"By exposing ACR1 to light, we have bridged the cell's own signalling chain, thus proving the hypothesis that the opening of anion channels is essential and sufficient for stomatal closure," Hedrich summarises the results of the study. The exposure to light had almost completely prevented the transpiration of the plants.

With this knowledge, it is now possible to cultivate plants with an increased number of anion channels in the guard cells. Plants equipped in this way should close their stomata more quickly in response to approaching heat waves and thus be better able to cope with periods of drought.

"Plant anion channels are activated during stress; this process is dependent on calcium. In a follow up optogenetics project, we want to use calcium-conducting channelrhodopsins to specifically allow calcium to flow into the guard cells cell through exposure to light and to understand the mechanism of anion channel activation in detail," Hedrich outlines the upcoming goals of his research.

Basic scientific research can also benefit from the results from Würzburg: "Our new optogenetic tool has enormous potential for research," says the JMU professor. "With it, we can gain new insights into how plants regulate their water consumption and how carbon dioxide fixation and stomatal movements are coupled."

We know that turning goals into a game can increase people's physical activity. We also know that financial incentives can be effective, especially when they're framed in a way where people lose money if they don't reach their goals. But a new Perelman School of Medicine at the University of Pennsylvania study adds to evidence that combining the two can result in significant gains.

Researchers affiliated with Penn Medicine's Center for Health Care Innovation showed that a group of veterans who were overweight or obese and receiving care from a Philadelphia hospital were able to increase their daily step counts by more than 1,200, on average, when their personalized goals were paired with a game in which they received support from a buddy, all while they stood to potentially lose reward money if they didn't hit their targets.

The research, believed to be the first of its kind among veterans, was published in JAMA Network Open.

"What our study begins to show is that the combination of varying approaches can be effective, but we need to learn more about the duration and ability to sustain an effect over longer-periods of time," said the study's lead author, Anish Agarwal, MD, a clinical innovation manager in the Penn Medicine Center for Digital Health and an assistant professor of Emergency Medicine.

Often, companies create programs to encourage healthier behavior among employees. These programs typically involve step counts measured by some form of pedometer and daily or weekly goals, but leave it at that. Agarwal believes that it's important to study how different framings of goals and the accomplishment of them is important to improving them and actually helping people improve their behaviors.

"The world of mobile and digital health has created an environment where rolling these programs out is easier and more interactive," Agarwal said. "Time will certainly tell in how these incentives can be used to in equitable and sustainable ways."

For this study, Agarwal and his fellow researchers - including senior author Mitesh Patel, MD, an associate professor of Medicine - recruited 180 participants. They were randomly assigned to one of three different, equal groups. Everyone, including those in the control group, received an electronic, wearable device to track steps and selected a personalized goal. But two of the groups utilized a behavioral science concept called "gamification," in which their goals were tied to a game in which they achieved points and levels for hitting their step goals. The progress of these participants was shared weekly via email with a buddy the participant had designated who could review them and encourage them.

One of those groups, though, had money riding on their goals. In total, they stood to make $120 if they hit their goals each week for the study's 12-week intervention period. Every week that they didn't achieve their goals, the participants lost $10 from the total they'd be issued at the end of the study.

It was this group, the researchers found, who made the largest strides during the intervention period. Compared to the control group, they significantly increased their steps by an average of 1,224. The other gamified group did increase their steps above the control group, but it was only by 433, which was not significant.

"Loss aversion is a very powerful motivator," Patel said. "Most programs deliver rewards after the goal is achieved, but this clinical trial, similar to previous ones, shows that offering financial upfront and letting participants know they can be an effective strategy."

After the 12-week intervention period ended, the researchers continued to observe participants' step counts when the games were turned off. In the eight weeks following, neither group sustained their progress compared to those who were not part of the games. The group with financial incentives did still have an average 564 step increase in their daily totals, but the non-incentive group actually decreased their daily steps by an average of 160.

Agarwal said that more research is needed to determine exactly why they got the results they did when research has supported gamification both with and without financial incentives. Their main focus is to increase the intervention time, and, ultimately, achieve longer term changes.

"Next steps for us are to begin to design and test approaches which help sustain the effect beyond the intervention period," Agarwal said. "One could imagine varying financial amounts at risk, duration of the intervention, and a strong social incentive. In this study the social incentive was passive, a weekly email to a social support person, but we could imagine more social connection or competition to test for individuals or groups."

What The Study Did: This survey study examined disparities in COVID-19 vaccine acceptance and approaches to improve vaccination rates among adults in China.

Authors: Jingjing Ma, Ph.D., of Peking University in Beijing, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/ 

(doi:10.1001/jamahealthforum.2021.1466)

Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

A research team co-led by UCL (University College London) has solved a decades-old mystery as to how Jupiter produces a spectacular burst of X-rays every few minutes.

The X-rays are part of Jupiter's aurora - bursts of visible and invisible light that occur when charged particles interact with the planet's atmosphere. A similar phenomenon occurs on Earth, creating the northern lights, but Jupiter's is much more powerful, releasing hundreds of gigawatts of energy, enough to briefly power all of human civilisation*.

In a new study, published in Science Advances, researchers combined close-up observations of Jupiter's environment by NASA's satellite Juno, which is currently orbiting the planet, with simultaneous X-ray measurements from the European Space Agency's XMM-Newton observatory (which is in Earth's own orbit).

The research team, led by UCL and the Chinese Academy of Sciences, discovered that X-ray flares were triggered by periodic vibrations of Jupiter's magnetic field lines. These vibrations create waves of plasma (ionised gas) that send heavy ion particles "surfing" along magnetic field lines until they smash into the planet's atmosphere, releasing energy in the form of X-rays.

Co-lead author Dr William Dunn (UCL Mullard Space Science Laboratory) said: "We have seen Jupiter producing X-ray aurora for four decades, but we didn't know how this happened. We only knew they were produced when ions crashed into the planet's atmosphere.

"Now we know these ions are transported by plasma waves - an explanation that has not been proposed before, even though a similar process produces Earth's own aurora. It could, therefore, be a universal phenomenon, present across many different environments in space."

X-ray auroras occur at Jupiter's north and south poles, often with clockwork regularity - during this observation Jupiter was producing bursts of X-rays every 27 minutes.

The charged ion particles that hit the atmosphere originate from volcanic gas pouring into space from giant volcanoes on Jupiter's moon, Io.

This gas becomes ionised (its atoms are stripped free of electrons) due to collisions in Jupiter's immediate environment, forming a donut of plasma that encircles the planet.

Co-lead author Dr Zhonghua Yao (Chinese Academy of Sciences, Beijing) said: "Now we have identified this fundamental process, there is a wealth of possibilities for where it could be studied next. Similar processes likely occur around Saturn, Uranus, Neptune and probably exoplanets as well, with different kinds of charged particles 'surfing' the waves."

Co-author Professor Graziella Branduardi-Raymont (UCL Mullard Space Science Laboratory) said: "X-rays are typically produced by extremely powerful and violent phenomena such as black holes and neutron stars, so it seems strange that mere planets produce them too.

"We can never visit black holes, as they are beyond space travel, but Jupiter is on our doorstep. With the arrival of the satellite Juno into Jupiter's orbit, astronomers now have a fantastic opportunity to study an environment that produces X-rays up close."

For the new study, researchers analysed observations of Jupiter and its surrounding environment carried out continuously over a 26-hour period by the Juno and XMM-Newton satellites.

They found a clear correlation between waves in the plasma detected by Juno and X-ray auroral flares at Jupiter's north pole recorded by X-MM Newton. They then used computer modelling to confirm that the waves would drive the heavy particles towards Jupiter's atmosphere.

Why the magnetic field lines vibrate periodically is unclear, but the vibration may result from interactions with the solar wind or from high-speed plasma flows within Jupiter's magnetosphere.

Jupiter's magnetic field is extremely strong - about 20,000 times as strong as Earth's - and therefore its magnetosphere, the area controlled by this magnetic field, is extremely large. If it was visible in the night sky, it would cover a region several times the size of our moon.

The work was supported by the Chinese Academy of Sciences, the National Natural Science Foundation of China, and the UK's Science and Technology Facilities Council (STFC), Royal Society, and Natural Environment Research Council, as well as ESA and NASA.

* Jupiter's X-ray aurora alone releases about a gigawatt, equivalent to what one power station might produce over a period of days.

A new study (the ATOMIC2 trial), presented at this year's European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) and published simultaneously in The Lancet Respiratory Medicine, shows the antimicrobial drug azithromycin - already approved for use in multiple infections - does not prevent mild COVID-19 cases progressing to hospitalisation or death.

The study, by Dr Timothy Hinks, John Radcliffe Hospital and University of Oxford, UK, and colleagues, shows that azithromycin should not be used as a treatment for COVID-19 and all countries must stop using it for this purpose, to prevent resistance developing to azithromycin in other infections.

The SARS-CoV-2 pandemic has not only started a rush to develop new treatments, but also investigations of already approved drugs to determine if they too can be used to treat COVID-19. Azithromycin is an antibiotic used to treat serious chest infections including pneumonias and drug-resistant tuberculosis, trachoma - a common preventable cause of blindness - sinus infections, Lyme disease, skin infections and some sexually transmitted infections such as chlamydia.

The antibacterial, anti-inflammatory and antiviral properties of azithromycin suggested it could have therapeutic potential against COVID-19. However, there is a lack of data from randomised controlled trials of azithromycin to treat mild-to-moderate COVID-19 disease. In this study, the authors assessed whether azithromycin is effective in reducing hospitalisation in patients with mild-to-moderate COVID-19. These were people with COVID-19 symptoms sufficiently severe to prompt them to seek hospital assessment, but not severe enough, initially, to require admission for oxygen therapy.

This randomised clinical trial at 19 centres in the UK enrolled adults aged 18 years and older, presenting to hospitals with clinically-diagnosed highly-probable or confirmed COVID-19 infection, with less than 14 days of symptoms, considered suitable for initial hospital assessment then treatment and/or observation at home. Patients were randomised (1:1) to azithromycin (500 mg daily orally for 14 days) or to observation at home only. The primary outcome was the difference in proportion of participants with death or hospital admission from any cause over the following 28 days.

A total of 298 participants were enrolled from June 2020 to January 2021 and 292 were included in the final analysis. The authors found no difference between the azithromycin and control groups in the risk of COVID-19 progressing to hospitalisation or death.

They explain that, in contrast to other studies the high dose of azithromycin in this new study (500 mg daily) and long duration (14 days) was selected to ensure that the trial adequately assessed potential antiviral, antibacterial and anti-inflammatory benefits. COVID-19 is considered to have a distinct early "viraemic" phase with a high viral load and a late inflammatory phase in some individuals, and therefore assessment of antiviral activity needed to be early in the disease course prior to onset of severe disease.

At the same time, it was not known what doses might be required to produce an adequate anti-inflammatory effect and so it was necessary to give a high dose of long duration to ensure the anti-inflammatory effect was tested throughout the late stage of innate/ acute phase of inflammatory cytokine dysregulation (known as the cytokine storm, which overwhelms the immune system of affected individuals and is often fatal).

The authors say: "In this trial of people with clinically-diagnosed mild-moderate COVID-19 managed without hospital admission, adding azithromycin to standard care treatment did not reduce the risk of subsequent hospitalisation or death, or of time to hospitalisation... this finding, taken together with clear negative results from other studies across the disease course from early, low risk patients, to severe hospitalised disease, provides strong confirmation that azithromycin is not effective in treating COVID-19. It is essential that clinicians worldwide stop using this medication as a treatment for COVID-19. We now know it is not effective against COVID-19 and we need urgently to protect against the very real threat of driving drug resistance to this precious class of antibiotics."

For interviews with the report authors, please contact Dr Waasila Jassat, National Institute for Communicable Diseases of the National Health Laboratory Service, South Africa E) waasilaj@nicd.ac.za T) +27(0)82 927 4138

Alternative contact in the ECCMID Press Room: Tony Kirby T) + 44(0)7834 385827 E) tony@tonykirby.com or Rachael Davies T) +44(0)797 456 0784 E) rachaelvdavies@hotmail.co.uk

Notes to editors:

[1] Wave 1: (14721 deaths/59617625 SA population)*100,000 = 24.7 deaths per 100,000 people
Wave 2: (28682 deaths/59617625 SA population)*100,000 = 48.1 deaths per 100,000 people

[2] Coronavirus deaths by country in Africa 2021 | Statista / South Africa | UNAIDS
https://www.statista.com/statistics/1170530/coronavirus-deaths-in-africa/

[3] See table 1; weeks with very high admissions; 27,949 deaths among 104,058 patients with outcomes (case fatality risk 26.9%). Weeks with low admissions; 8,985 deaths among 50,840 patients with outcomes (case fatality risk 17.7%).

The surveillance was funded by the National Institute for Communicable Diseases and the South African Government. The study did not receive any additional funding.

The authors declare no conflicts of interest.

The Lancet Global Health: Difference in mortality among individuals admitted to hospital with COVID-19 during the first and second waves in South Africa: a cohort study

Article available under embargo at (journalist only link):
http://www.thelancet-press.com/embargo/tlgh.pdf

Appendix available under embargo at (journalist only link):
http://www.thelancet-press.com/embargo/tlghAPPX.pdf

NOTE: THE ABOVE LINK IS FOR JOURNALISTS ONLY AND WILL BE DEACTIVATED AFTER THE EMBARGO LIFTS. IF YOU WISH TO PROVIDE A LINK TO THIS PAPER FOR YOUR READERS, PLEASE USE THE FOLLOWING, WHICH WILL GO LIVE WHEN THE EMBARGO LIFTS:

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Journal

The Lancet Global Health

Although Covid-19 affects men and women differently, the large majority of current clinical studies of SARS-CoV-2 and COVID-19 makes no mention of sex/gender. Indeed, only a fraction, 4 percent, explicitly plan to address sex and gender in their analysis, concludes a new analysis of nearly 4,500 studies. 21 percent only take this variable into account when selecting participants while 5.4 % go as far as planning to have sex-matched or representative subgroups and samples. The article is published in Nature Communications.

During the corona pandemic, differences can be observed between men and women. Men are more vulnerable to a severe course of COVID-19; more men are hospitalized, and more men die from the effects of the virus. Why that is, we do not know exactly yet, but the consequence of the difference may be that men and women might need different therapies. At the same time, gender is connected to the risk of infection, for example because women more commonly are employed in positions with client or customer contact, or as care-givers, increasing the risk of exposure. This calls for attention to both dimensions in the conduction of clinical trials and planning public health measures.

Still, only a minority of 4,420 registered clinical studies on COVID-19 mention sex/gender in the study registration, a new analysis published in Nature Communications shows. The study is conducted by researchers at Nijmegen's Radboud University Medical Center, Aarhus University, University of Copenhagen and University of Bielefeld.

According to the last author of the article, Sabine Oertelt-Prigione from Radboud University and at the Medical School of the University of Bielefeld, the lacking consideration of sex and gender is problematic: "We have seen from the beginning that the disease does not have an identical course for women and men. The differences in rates of hospitalization and death point to this. This means that our care, such as medicines or other interventions, could also have a different outcome depending on whether the patient is a woman or a man."

Only 4 percent of studies registered plan to explicitly include sex as a variable in their analysis

The researchers looked at 4,420 COVID-19 studies registered with ClinicalTrials.gov, a U.S. database of more than 300,000 studies from 200 countries. In the COVID-19 sample, 1,659 were observational studies, and 2,475 were intervention studies.

Of these 4,420 registered studies, 935 (21.2%) explicitly addressed sex/gender solely as a recruitment criterion and only 178 (4%) mentioned sex/gender as a planned analytical variable. A further 237 (5.4%) planned sex-matched or representative samples (65) or emphasized sex/gender reporting (172). 124 studies (2.8%) focused solely on one sex, with 100 recruiting only female participants and 24 only male ones. Female-only studies mostly focused on the relation between COVID-19 and pregnancy outcomes.

Research under time pressure

A reason for not including data on sex and gender may be that the studies are conducted under high time pressure. Sabine Oertelt-Prigione: "Researchers are sometimes worried that analyzing sex differences in a study might mean more participants and longer recruitment times to reach their targets. Especially in the early phases of the pandemic, they were working under lots of time pressure ".

Emer Brady, first author of the study and working at the Danish Center for Studies in Research and Research Policy at Aarhus University supplements with: "On the subject of time pressures, we did hope that as the pandemic wore on and more awareness was raised about the sex and gender disparities we would see more of a focus on sex and gender in the study protocols being registered on ClinicalTrials.gov, but that turned out not to be the case. We also looked at the published trials, where the attention to sex and gender was higher, but still only one in four trials accounted for or reported sex or gender in their analyses."

Oertelt-Prigione emphasizes the importance of sex and genders role in clinical research: "We increasingly see that men and women respond differently to pharmacological interventions. Ignoring this in trials might lead to serious unwanted side effects later. Looking at sex differences has helped us understand the infection better and it will help us understand our treatment options better. Taking into consideration sex differences is an essential step toward more personalized healthcare."

Tokyo, Japan - Scientists from The University of Tokyo Institute of Industrial Science have designed a machine learning algorithm to predict the size of an individual cell as it grows and divides. By using an artificial neural network that does not impose the assumptions commonly employed in biology, the computer was able to make more complex and accurate forecasts than previously possible. This work may help advance the field of quantitative biology as well as improve the industrial production of medications or fermented products.

As in all of the natural sciences, biology has developed mathematical models to help fit data and make predictions about the future. However, because of the inherent complexities of living systems, many of these equations rely on simplifying assumptions that do not always reflect the actual underlying biological processes. Now, researchers at The University of Tokyo Institute of Industrial Science have implemented a machine learning algorithm that can use the measured size of single cells over time to predict their future size. Because the computer automatically recognizes patterns in the data, it is not constrained like conventional methods.

"In biology, simple models are often used based on their capacity to reproduce the measured data," first author Atsushi Kamimura says. "However, the models may fail to capture what is really going on because of human preconceptions,".

The data for this latest study were collected from either an Escherichia coli bacterium or a Schizosaccharomyces pombe yeast cell held in a microfluidic channel at various temperatures. The plot of size over time looked like a "sawtooth" as exponential growth was interrupted by division events. Human biologists usually use a "sizer" model, based on the absolute size of the cell, or "adder" model, based on the increase in size since birth, to predict when divisions will occur. The computer algorithm found support for the "adder" principle, but as part of a complex web of biochemical reactions and signaling.

"Our deep-learning neural network can effectively separate the history-dependent deterministic factors from the noise in given data," senior author Tetsuya Kobayashi says.

This method can be extended to many other aspects of biology besides predicting cell size. In the future, life science may be driven more by objective artificial intelligence than human models. This may lead to more efficient control of microorganisms we use to ferment products and produce drugs.

Split liver transplantation (SLT) provides an opportunity to divide a donor liver and offer transplants to two small patients, one or both of whom could be a child. SLT, which is underused in the United States, could be used more widely to decrease the number of deaths of people on transplant waiting lists. In a new article, researchers address some of the ethical decisions that go into decisions to split a liver and provide a model to help hospitals make SLT decisions.

The article, by researchers at Carnegie Mellon University (CMU), appears in The BMJ, which is published by the Institute of Medical Ethics.

"Should a large liver always be split if it is medically safe to do so?" asks Sridhar Tayur, Professor of Operations Management at CMU's Tepper School of Business, who coauthored the article. "We say not always, and clarify under what circumstances SLT is ethically desirable."

Both the Organ Procurement and Transplant Network and the United Network for Organ Sharing have identified SLT as an important ethical issue. To flesh out the issues at play, the authors - including UCSF Transplant Surgeon, John Roberts who previously served as UNOS President - present several case studies regarding what to do with a large liver available for transplantation when recipients are different sizes and ages and have different levels of need.

Using philosophical theory, the authors - that include Alan Strudler, an ethicist from University of Pennsylvania -- address considerations that limit transplantation of portions of the liver. SLT requires that the relative size of the donor and the recipient match because if the portion of the liver is too small for the recipient, it will fail. The most common split results in one part of the liver that is about 75 percent of the original mass (typically transplanted to an adult) and one part that is 25 percent (typically transplanted to a child). However, the larger part may be inadequate for a large adult, and splitting raises logistical issues, such as preparing two recipients in the same operating room, the time and expertise needed to split the liver, and the transportation of the parts of the liver.

The authors suggest that hospitals use a flexible decision support model to allow for analyses that ask "what if" questions about the patients who need transplants and how their needs are changing. The model should consider various metrics of fairness and efficiency. For example, the medical community should reach reasonable consensus about what items constitute fairness, including patients' scores on measures of the severity of liver cirrhosis, which prioritize decisions about transplantation; waiting time until transplant; and likelihood of death.

"Much of the ethics involved in SLT suggest a dynamic problem whose answer requires a dynamic solution," explains Tae Wan Kim, Associate Professor of Business Ethics at CMU's Tepper School of Business, who coauthored the study. "The problem of liver transplantation is dynamic, so the solution must be dynamic and oscillate qualitatively between different demographics."

As an example of a dynamic allocation policy, decisions about SLT would oscillate between splitting a large liver if the health of the small patients involved were worse than that of the large patient and not splitting the liver if the opposite were true.

Research has shown that listening to music daily improves language recovery in patients who have experienced a stroke. However, the neural mechanisms underlying the phenomenon have so far remained unknown.

A study conducted at the University of Helsinki and the Turku University Hospital Neurocenter compared the effect of listening to vocal music, instrumental music and audiobooks on the structural and functional recovery of the language network of patients who had suffered an acute stroke. In addition, the study investigated the links between such changes and language recovery during a three-month follow-up period. The study was published in the eNeuro journal.

Based on the findings, listening to vocal music improved the recovery of the structural connectivity of the language network in the left frontal lobe compared to listening to audiobooks. These structural changes correlated with the recovery of language skills.

"For the first time, we were able to demonstrate that the positive effects of vocal music are related to the structural and functional plasticity of the language network. This expands our understanding of the mechanisms of action of music-based neurological rehabilitation methods," says Postdoctoral Researcher Aleksi Sihvonen.

Listening to music supports other rehabilitation

Aphasia, a language impairment resulting from a stroke, causes considerable suffering to patients and their families. Current therapies help in the rehabilitation of language impairments, but the results vary and the necessary rehabilitation is often not available to a sufficient degree and early enough.

"Listening to vocal music can be considered a measure that enhances conventional forms of rehabilitation in healthcare. Such activity can be easily, safely and efficiently arranged even in the early stages of rehabilitation," Sihvonen says.

According to Sihvonen, listening to music could be used as a cost-efficient boost to normal rehabilitation, or for rehabilitating patients with mild speech disorders when other rehabilitation options are scarce.

After a disturbance of the cerebral circulation, the brain needs stimulation to recover as well as possible. This is the goal of conventional rehabilitation methods as well.

"Unfortunately, a lot of the time spent in hospital is not stimulating. At these times, listening to music could serve as an additional and sensible rehabilitation measure that can have a positive effect on recovery, improving the prognosis," Sihvonen adds.

Mitochondria, the powerhouse of the cell, convert sustenance into energy, fueling the cell's activities. In addition to power, mitochondria also produce reactive oxygen species, byproduct molecules primed to help facilitate communication among the other units in the cells. But when produced too abundantly, they damage DNA and render some cellular components dysfunctional. Now, an international research team has revealed how mitochondria keep their reactive oxygen species production in check.

They published their results on June 30 in Frontiers in Cell and Developmental Biology.

"Excessive generation of reactive oxygen species in mitochondria damages mitochondria and reduces cell function, so the mechanism by which mitochondria maintain production of reactive oxygen species is crucial for cells," said lead paper author Yoshihiro Ohta, associate professor in the Department of Biotechnology and Life Science at Tokyo University of Agriculture and Technology in Japan. "In this study, we found that mitochondria have a mechanism to spontaneously avoid the production of excess reactive oxygen species."

Mitochondria are double membraned, with genetic information and functional units contained within its internal matrix. Mitochondria convert chemical energy into power for the cell by moving protons from outside to inside the matrix with the help of an enzyme responsible for energy conversion. But mitochondria also appear to impulsively and temporarily take up protons through another protein through a process called spontaneous transient depolarization.

"Spontaneous fluctuations in mitochondrial membrane potential are physiological phenomena observed in a wide range of cells from plants to mammals," said Ohta. "In this study, we investigated how this spontaneous fluctuation occurs and what it is useful for."

The researchers found that increasing the pH of the matrix from neutral to basic significantly increased reactive oxygen species production. They also found that inhibition of the spontaneous fluctuation, or depolarization, increased both the matrix pH and presence of reactive oxygen species.

"Spontaneous transient depolarization may decrease reactive oxygen species production in the mitochondria by inhibiting sustained matrix pH elevation," Ohta said. "This is the first study suggesting the relationship between spontaneous transient depolarization and reactive oxygen species production."

While the researchers have not fully elucidated the mechanism by which mitochondria control their reactive oxygen species production, they did propose a model suggesting that spontaneous transient depolarization occurs when increased matrix pH facilitates moving more protons from outside the matrix into the matrix.

The researchers plan to further investigate the mechanism to understand not only how mitochondria can prevent overproduction of reactive oxygen species, but also if detecting the spontaneous fluctuation in mitochondria could indicate the oxidative stress state -- and damage -- of cells.