"Best Paper" awards lack transparency, inclusivity, and support for Open Science.

Awards can propel academic careers. They also reflect the culture and values of the scientific community. But do awards incentivize greater transparency, inclusivity, and openness in science? Our cross-disciplinary survey of 222 awards for the "best" journal articles across all 27 SCImago subject areas revealed that journals and learned societies administering such awards generally publish little detail on their procedures and criteria. Award descriptions were brief, rarely including contact details or information on the nominations pool. Nominations of underrepresented groups were not explicitly encouraged, and concepts that align with Open Science were almost absent from the assessment criteria. At the same time, 10% of awards, especially the recently established ones, tended to use article-level impact metrics. USA-affiliated researchers dominated the winner's pool (48%), while researchers from the Global South were uncommon (11%). Sixty-one percent of individual winners were men. Overall, Best Paper awards miss the global calls for greater transparency and equitable access to academic recognition. We provide concrete and implementable recommendations for scientific awards to improve the scientific recognition system and incentives for better scientific practice.

Development and Evaluation of a Framework for Identifying and Addressing Spin for Harms in Systematic Reviews of Interventions.

"Spin" refers to misleading reporting, interpretation, and extrapolation of findings in primary and secondary research (such as in systematic reviews). The study of spin primarily focuses on beneficial outcomes. The objectives of this research were threefold: first, to develop a framework for identifying spin associated with harms in systematic reviews of interventions; second, to apply the framework to a set of reviews, thereby pinpointing instances where spin may be present; and finally, to revise the spin examples, offering guidance on how spin can be rectified.The authors developed their framework through an iterative process that engaged an international group of researchers specializing in spin and reporting bias. The framework comprises 12 specific types of spin for harms, grouped by 7 categories across the 3 domains (reporting, interpretation, and extrapolation). The authors subsequently gathered instances of spin from a random sample of 100 systematic reviews of interventions. Of the 58 reviews that assessed harm and the 42 that did not, they found that 28 (48%) and 6 (14%), respectively, had at least 1 of the 12 types of spin for harms. Inappropriate extrapolation of the results and conclusions for harms to populations, interventions, outcomes, or settings not assessed in a review was the most common category of spin in 17 of 100 reviews.The authors revised the examples to remove spin, taking into consideration the context (for example, medical discipline, source population), findings for harms, and methodological limitations of the original reviews. They provide guidance for authors, peer reviewers, and editors in recognizing and rectifying or (preferably) avoiding spin, ultimately enhancing the clarity and accuracy of harms reporting in systematic review publications.

POLR3B is associated with a developmental and epileptic encephalopathy with myoclonic-atonic seizures and ataxia.

OBJECTIVE: POLR3B encodes the second largest subunit of RNA polymerase III, which is essential for transcription of small non-coding RNAs. Biallelic pathogenic variants in POLR3B are associated with an inherited hypomyelinating leukodystrophy. Recently, de novo heterozygous variants in POLR3B were reported in six individuals with ataxia, spasticity, and demyelinating peripheral neuropathy. Three of these individuals had epileptic seizures. The aim of this article is to precisely define the epilepsy phenotype associated with de novo heterozygous POLR3B variants. METHODS: We used online gene-matching tools to identify 13 patients with de novo POLR3B variants. We systematically collected genotype and phenotype data from clinicians using two standardized proformas. RESULTS: All 13 patients had novel POLR3B variants. Twelve of 13 variants were classified as pathogenic or likely pathogenic as per American College of Medical Genetics (ACMG) criteria. Patients presented with generalized myoclonic, myoclonic-atonic, atypical absence, or tonic-clonic seizures between the ages of six months and 4 years. Epilepsy was classified as epilepsy with myoclonic-atonic seizures (EMAtS) in seven patients and "probable EMAtS" in two more. Seizures were treatment resistant in all cases. Three patients became seizure-free. All patients had some degree of developmental delay or intellectual disability. In most cases developmental delay was apparent before the onset of seizures. Three of 13 cases were reported to have developmental stagnation or regression in association with seizure onset. Treatments for epilepsy that were reported by clinicians to be effective were: sodium valproate, which was effective in five of nine patients (5/9) who tried it; rufinamide (2/3); and ketogenic diet (2/3). Additional features were ataxia/incoordination (8/13); microcephaly (7/13); peripheral neuropathy (4/13), and spasticity/hypertonia (6/13). SIGNIFICANCE: POLR3B is a novel genetic developmental and epileptic encephalopathy (DEE) in which EMAtS is the predominant epilepsy phenotype. Ataxia, neuropathy, and hypertonia may be variously observed in these patients.

Epidemiology and reporting characteristics of preclinical systematic reviews.

In an effort to better utilize published evidence obtained from animal experiments, systematic reviews of preclinical studies are increasingly more common-along with the methods and tools to appraise them (e.g., SYstematic Review Center for Laboratory animal Experimentation [SYRCLE's] risk of bias tool). We performed a cross-sectional study of a sample of recent preclinical systematic reviews (2015-2018) and examined a range of epidemiological characteristics and used a 46-item checklist to assess reporting details. We identified 442 reviews published across 43 countries in 23 different disease domains that used 26 animal species. Reporting of key details to ensure transparency and reproducibility was inconsistent across reviews and within article sections. Items were most completely reported in the title, introduction, and results sections of the reviews, while least reported in the methods and discussion sections. Less than half of reviews reported that a risk of bias assessment for internal and external validity was undertaken, and none reported methods for evaluating construct validity. Our results demonstrate that a considerable number of preclinical systematic reviews investigating diverse topics have been conducted; however, their quality of reporting is inconsistent. Our study provides the justification and evidence to inform the development of guidelines for conducting and reporting preclinical systematic reviews.

Photochromic Ln-MOFs: A Platform for Metal-Photoswitch Cooperativity.

Optoelectronic devices based on lanthanide-containing materials are an emergent area of research due to imminent interest in a new generation of diode materials, optical and magnetic sensors, and ratiometric thermometers. Tailoring material properties through the employment of photo- or thermochromic moieties is a powerful approach that requires a deep fundamental understanding of possible cooperativity between lanthanide-based metal centers and integrated switchable units. In this work, we probe this concept through the synthesis, structural analysis, and spectroscopic characterization of novel photochromic lanthanide-based metal-organic materials containing noncoordinatively integrated photoresponsive 4,4'-azopyridine between lanthanide-based metal centers. As a result, a photophysical material response tailored on demand through the incorporation of photochromic compounds within a rigid matrix was investigated. The comprehensive analysis of photoresponsive metal-organic materials includes single-crystal X-ray diffraction and diffuse reflectance spectroscopic studies that provide guiding principles necessary for understanding photochromic unit-lanthanide-based metal-organic framework (MOF) cooperativity. Furthermore, steady-state and time-resolved diffuse reflectance spectroscopic studies revealed a rapid rate of photoresponsive moiety attenuation upon its integration within the rigid matrix of lanthanide-based MOFs in comparison with that in solution, highlighting a unique role and synergy that occurred between stimuli-responsive moieties and the lanthanide-based MOF platform, allowing for tunability and control of material photoisomerization kinetics.

Patterns in the Use of Emergency Telemedicine Support in the Management of Traumatic Road Crashes.

Objective: The introduction of emergency telemedicine care models is a common theme in health jurisdictions that include rural and remote populations. How the availability of these models influences the way clinicians manage traumatic road crashes is not yet fully understood. This study seeks to compare road crashes where telemedicine was and was not used and to identify any variables that may increase the likelihood of telemedicine usage by treating clinicians. Methods: Road crashes reported in the state Department of Transport and Main Roads (Queensland, Australia) crash database between January 1, 2019, and November 30, 2020 (n = 23,734) were compared to videoconferencing call logs to determine which crashes resulted in treatment that was supported by telemedicine (n = 204). Analysis was performed to examine differences in characteristics related to the crash depending on whether telemedicine support was requested. Results: Road crashes where telemedicine support was requested on average involved more casualties (1.6 vs. 1.41; t(11,287) = -3.26, p < 0.001, relative risk = 1.13). Crashes that occurred in rural settings accounted for most requests for telemedicine (65.68%; X2 = 159.2, p < 0.001) and a greater percentage of crashes in remote locations (3.36% vs. 2.35%; X2 = 256.97, p < 0.001, relative risk = 1.43). The use of telemedicine support for crashes was associated with a 13% increase in the mean number of casualties, compared to crashes where telemedicine support was not used. Conclusion: Telemedicine support is requested by clinicians providing emergency treatment in the management of road crashes that produce more severe injuries, involve multiple casualties, and take place in more rural settings or remote locations.

Splinting for carpal tunnel syndrome.

BACKGROUND: Carpal tunnel syndrome (CTS) is a compression neuropathy of the median nerve causing pain and numbness and tingling typically in the thumb, index and middle finger. It sometimes results in muscle wasting, diminished sensitivity and loss of dexterity. Splinting the wrist (with or without the hand) using an orthosis is usually offered to people with mild-to-moderate findings, but its effectiveness remains unclear. OBJECTIVES: To assess the effects (benefits and harms) of splinting for people with CTS. SEARCH METHODS: On 12 December 2021, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, AMED, CINAHL, ClinicalTrials.gov, and WHO ICTRP with no limitations. We checked the reference lists of included studies and relevant systematic reviews for studies. SELECTION CRITERIA: Randomised trials were included if the effect of splinting could be isolated from other treatment modalities. The comparisons included splinting versus no active treatment (or placebo), splinting versus another disease-modifying non-surgical treatment, and comparisons of different splint-wearing regimens. We excluded studies comparing splinting with surgery or one splint design with another. We excluded participants if they had previously undergone surgical release. DATA COLLECTION AND ANALYSIS: Review authors independently selected trials for inclusion, extracted data, assessed study risk of bias and the certainty in the body of evidence for primary outcomes using the GRADE approach, according to standard Cochrane methodology. MAIN RESULTS: We included 29 trials randomising 1937 adults with CTS. The trials ranged from 21 to 234 participants, with mean ages between 42 and 60 years. The mean duration of CTS symptoms was seven weeks to five years. Eight studies with 523 hands compared splinting with no active intervention (no treatment, sham-kinesiology tape or sham-laser); 20 studies compared splinting (or splinting delivered along with another non-surgical intervention) with another non-surgical intervention; and three studies compared different splinting regimens (e.g. night-time only versus full time). Trials were generally at high risk of bias for one or more domains, including lack of blinding (all included studies) and lack of information about randomisation or allocation concealment in 23 studies. For the primary comparison, splinting compared to no active treatment, splinting may provide little or no benefits in symptoms in the short term (< 3 months). The mean Boston Carpal Tunnel Questionnaire (BCTQ) Symptom Severity Scale (SSS) (scale 1 to 5, higher is worse; minimal clinically important difference (MCID) 1 point) was 0.37 points better with splint (95% confidence interval (CI) 0.82 better to 0.08 worse; 6 studies, 306 participants; low-certainty evidence) compared with no active treatment. Removing studies with high or unclear risk of bias due to lack of randomisation or allocation concealment supported our conclusion of no important effect (mean difference (MD) 0.01 points worse with splint; 95% CI 0.20 better to 0.22 worse; 3 studies, 124 participants). In the long term (> 3 months), we are uncertain about the effect of splinting on symptoms (mean BCTQ SSS 0.64 better with splinting; 95% CI 1.2 better to 0.08 better; 2 studies, 144 participants; very low-certainty evidence). Splinting probably does not improve hand function in the short term and may not improve hand function in the long term. In the short term, the mean BCTQ Functional Status Scale (FSS) (1 to 5, higher is worse; MCID 0.7 points) was 0.24 points better (95% CI 0.44 better to 0.03 better; 6 studies, 306 participants; moderate-certainty evidence) with splinting compared with no active treatment. In the long term, the mean BCTQ FSS was 0.25 points better (95% CI 0.68 better to 0.18 worse; 1 study, 34 participants; low-certainty evidence) with splinting compared with no active treatment. Night-time splinting may result in a higher rate of overall improvement in the short term (risk ratio (RR) 3.86, 95% CI 2.29 to 6.51; 1 study, 80 participants; number needed to treat for an additional beneficial outcome (NNTB) 2, 95% CI 2 to 2; low-certainty evidence).  We are uncertain if splinting decreases referral to surgery, RR 0.47 (95% CI 0.14 to 1.58; 3 studies, 243 participants; very low-certainty evidence).  None of the trials reported health-related quality of life. Low-certainty evidence from one study suggests that splinting may have a higher rate of adverse events, which were transient, but the 95% CIs included no effect. Seven of 40 participants (18%) reported adverse effects in the splinting group and 0 of 40 participants (0%) in the no active treatment group (RR 15.0, 95% CI 0.89 to 254.13; 1 study, 80 participants).  There was low- to moderate-certainty evidence for the other comparisons: splinting may not provide additional benefits in symptoms or hand function when given together with corticosteroid injection (moderate-certainty evidence) or with rehabilitation (low-certainty evidence); nor when compared with corticosteroid (injection or oral; low certainty), exercises (low certainty), kinesiology taping (low certainty), rigid taping (low certainty), platelet-rich plasma (moderate certainty), or extracorporeal shock wave treatment (moderate certainty). Splinting for 12 weeks may not be better than six weeks, but six months of splinting may be better than six weeks of splinting in improving symptoms and function (low-certainty evidence). AUTHORS' CONCLUSIONS: There is insufficient evidence to conclude whether splinting benefits people with CTS. Limited evidence does not exclude small improvements in CTS symptoms and hand function, but they may not be clinically important, and the clinical relevance of small differences with splinting is unclear. Low-certainty evidence suggests that people may have a greater chance of experiencing overall improvement with night-time splints than no treatment. As splinting is a relatively inexpensive intervention with no plausible long-term harms, small effects could justify its use, particularly when patients are not interested in having surgery or injections. It is unclear if a splint is optimally worn full time or at night-time only and whether long-term use is better than short-term use, but low-certainty evidence suggests that the benefits may manifest in the long term.

Do brushings taken during bronchoscopy for suspected primary lung cancer increase diagnostic yield? An audit of real-world clinical practice.

We reviewed clinical records to determine whether the use of bronchial brushings improved diagnostic yield in a setting where bronchoscopy for suspected primary lung cancer is routinely guided by prior chest computed tomography but endobronchial ultrasound-guided sampling is unavailable. For 29% of cases who had brushings and at least one other test taken (bronchial biopsies or washings), the histological diagnosis was made solely on the basis of samples obtained by brushings.

How often do cancer researchers make their data and code available and what factors are associated with sharing?

BACKGROUND: Various stakeholders are calling for increased availability of data and code from cancer research. However, it is unclear how commonly these products are shared, and what factors are associated with sharing. Our objective was to evaluate how frequently oncology researchers make data and code available and explore factors associated with sharing. METHODS: A cross-sectional analysis of a random sample of 306 cancer-related articles indexed in PubMed in 2019 which studied research subjects with a cancer diagnosis was performed. All articles were independently screened for eligibility by two authors. Outcomes of interest included the prevalence of affirmative sharing declarations and the rate with which declarations connected to data complying with key FAIR principles (e.g. posted to a recognised repository, assigned an identifier, data license outlined, non-proprietary formatting). We also investigated associations between sharing rates and several journal characteristics (e.g. sharing policies, publication models), study characteristics (e.g. cancer rarity, study design), open science practices (e.g. pre-registration, pre-printing) and subsequent citation rates between 2020 and 2021. RESULTS: One in five studies declared data were publicly available (59/306, 19%, 95% CI: 15-24%). However, when data availability was investigated this percentage dropped to 16% (49/306, 95% CI: 12-20%), and then to less than 1% (1/306, 95% CI: 0-2%) when data were checked for compliance with key FAIR principles. While only 4% of articles that used inferential statistics reported code to be available (10/274, 95% CI: 2-6%), the odds of reporting code to be available were 5.6 times higher for researchers who shared data. Compliance with mandatory data and code sharing policies was observed in 48% (14/29) and 0% (0/6) of articles, respectively. However, 88% of articles (45/51) included data availability statements when required. Policies that encouraged data sharing did not appear to be any more effective than not having a policy at all. The only factors associated with higher rates of data sharing were studying rare cancers and using publicly available data to complement original research. CONCLUSIONS: Data and code sharing in oncology occurs infrequently, and at a lower rate than would be expected given the prevalence of mandatory sharing policies. There is also a large gap between those declaring data to be available, and those archiving data in a way that facilitates its reuse. We encourage journals to actively check compliance with sharing policies, and researchers consult community-accepted guidelines when archiving the products of their research.

Towards realizing the vision of precision medicine: AI based prediction of clinical drug response.

Accurate and individualized prediction of response to therapies is central to precision medicine. However, because of the generally complex and multifaceted nature of clinical drug response, realizing this vision is highly challenging, requiring integrating different data types from the same individual into one prediction model. We used the anti-epileptic drug brivaracetam as a case study and combine a hybrid data/knowledge-driven feature extraction with machine learning to systematically integrate clinical and genetic data from a clinical discovery dataset (n = 235 patients). We constructed a model that successfully predicts clinical drug response [area under the curve (AUC) = 0.76] and show that even with limited sample size, integrating high-dimensional genetics data with clinical data can inform drug response prediction. After further validation on data collected from an independently conducted clinical study (AUC = 0.75), we extensively explore our model to gain insights into the determinants of drug response, and identify various clinical and genetic characteristics predisposing to poor response. Finally, we assess the potential impact of our model on clinical trial design and demonstrate that, by enriching for probable responders, significant reductions in clinical study sizes may be achieved. To our knowledge, our model represents the first retrospectively validated machine learning model linking drug mechanism of action and the genetic, clinical and demographic background in epilepsy patients to clinical drug response. Hence, it provides a blueprint for how machine learning-based multimodal data integration can act as a driver in achieving the goals of precision medicine in fields such as neurology.