bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kidney transplant program specific reporting and transplant metrics
Authors: Andreoni Kenneth A. 
Published: December 2021

Purpose of review
Kidney transplantation is a heavily regulated medical procedure with the Secretary of HHS ultimately responsible for oversight and authority derived from the NOTA and the Final Rule. Transplant Programs undergo publicly reported evaluations every 6 months based on outcomes from a 2-and-a-half-year period. The current Bayesian metrics for kidney transplant programs were created such that over ten percentage of programs are deemed underperformers, or ‘flag’, every 6 months. Newly suggested transplant metrics have been released for public comment in Summer 2021. In addition to graft outcomes, waiting list mortality and organ acceptance rate ratios are proposed.

Recent findings
Under the newly proposed kidney transplant metrics, over 10% of programs are expected to be deemed underperformers or ‘flagged’. Transplant Center flagging is well correlated with decreased transplantation due to the transplant centres move to more conservative organ and patient acceptance. Death on the waiting list is a proposed metric over which transplant centres have little influence.

Summary
In the USA, the harsh regulation continued by Health Resources and Services Administration (HRSA) through the national organ procurement and transplant network (OPTN) and Scientific Registry for Transplant Recipients (SRTR) leads directly to high organ discard rates and limitations to transplanting patients with perceived unadjusted risks. Instead of loosening regulation in a highly functioning industry that achieves remarkable outcomes in end stage kidney patients, the OPTN with the SRTR persist in increasing potential penalties through more proposed metrics that continue to deem 10% of US kidney transplant programs as underperformers. HRSA must establish a reasonable regulatory environment that allows for innovation and increased transplant opportunities for US end-stage renal disease patients.
Bilateral vestibulopathy: the causes, diagnosis, and treatments
Authors: Kim Ji-Soo , Kim Hyo-Jung 
Published: December 2021

Purpose of review
The current review covers recent advances in bilateral vestibulopathy (BVP) in terms of its etiology, diagnosis, and treatments.

Recent findings
The etiology of BVP depends on its clinical course and associated findings, and genetic abnormalities are increasingly recognized in isolated as well as complicated form of BVP. Recent developments in evaluation of the vestibular function have greatly enhanced the detection of BVP, and introduction of the consensus diagnostic criteria by Barany Society has facilitated research on BVP. Vestibular prosthesis may improve vestibular function, posture, gait and quality of life in patients with BVP and would expand the therapeutic options for BVP in near future.

Summary
Genetics is expanding its role in identifying the causes of BVP of hitherto unknown etiology. The detection and investigation of BVP have been greatly enhanced by introduction of consensus diagnostic criteria and recent developments in methodology evaluating the vestibular function. Vestibular prothesis appears promising in managing BVP.

Video abstract

http://links.lww.com/CONR/A59.
Conditional Freezing, Flight and Darting?
Authors: Trott Jeremy M. , Hoffman Ann N. , Zhuravka Irina , Fanselow Michael S. 
Published: December 2021

AbstractFear conditioning is one of the most frequently used laboratory procedures for modeling learning and memory generally, and anxiety disorders in particular. The conditional response (CR) used in the majority of fear conditioning studies in rodents is freezing. Recently, it has been reported that under certain conditions, running, jumping or darting replaces freezing as the dominant CR. These findings raise both a critical methodological problem and an important theoretical issue. If only freezing is measured but rodents express their learning with a different response, then significant instances of learning, memory, or fear may be missed. In terms of theory, whatever conditions lead to these different behaviors may be a key to how animals transition between different defensive responses and different emotional states. We replicated these past results but along with several novel control conditions. Contrary to the prior conclusions, running and darting were entirely a result of nonassociative processes and were actually suppressed by associative learning. Darting and flight were taken to be analogous to nonassociative startle or alpha responses that are potentiated by fear. On the other hand, freezing was the purest reflection of associative learning. We also uncovered a rule that describes when these movements replace freezing: When afraid, freeze until there is a sudden novel change in stimulation, then burst into vigorous flight attempts. This rule may also govern the change from fear to panic.
HAVAs: Alzheimer’s Disease Detection using Normative and Pathological Lifespan Models
Authors: Coupé Pierrick , Manjón José V. , Mansencal Boris , Tourdias Thomas , Catheline Gwenaëlle , Planche Vincent 
Published: December 2021

AbstractIn this paper, we present an innovative MRI-based method for Alzheimer’s Disease (AD) detection and mild cognitive impairment (MCI) prognostic, using lifespan trajectories of brain structures. After a full screening of the most discriminant structures between AD and normal aging based on MRI volumetric analysis of 3032 subjects, we propose a novel Hippocampal-Amygdalo-Ventricular Alzheimer score (HAVAs) based on normative lifespan models and AD lifespan models. During a validation on three external datasets on 1039 subjects, our approach showed very accurate detection (AUC ≥ 94%) of patients with AD compared to control subjects and accurate discrimination (AUC=78%) between progressive MCI and stable MCI (during a 3 years follow-up). Compared to normative modelling and recent state-of-the-art deep learning methods, our method demonstrated better classification performance. Moreover, HAVAs simplicity makes it fully understandable and thus well-suited for clinical practice or future pharmaceutical trials.
A Non-Negative Matrix Tri-Factorization based Method for Predicting Antitumor Drug Sensitivity
Authors: Pidò Sara , Testa Carolina , Pinoli Pietro 
Published: December 2021

AbstractLarge annotated cell line collections have been proven to enable the prediction of drug response in the preclinical setting. We present an enhancement of Non-Negative Matrix Tri-Factorization method, which allows the integration of different data types for the prediction of missing associations. To test our method we retrieved a dataset from CCLE, containing the connections among cell lines and drugs by means of their IC50 values. We performed two different kind of experiments: a) prediction of missing values in the matrix, b) prediction of the complete drug profile of a new cell line, demonstrating the validity of the method in both scenarios.
Ropinirole hydrochloride for amyotrophic lateral sclerosis: A single-center, randomized feasibility, double-blind, placebo-controlled trial
Authors: Morimoto Satoru , Takahashi Shinichi , Ito Daisuke , Daté Yugaku , Okada Kensuke , Chyi Chai Muh , Nishiyama Ayumi , Suzuki Naoki , Fujimori Koki , Takao Masaki , Hirai Miwa , Kabe Yasuaki , Suematsu Makoto , Jinzaki Masahiro , Aoki Masashi , Fujiki Yuto , Sato Yasunori , Suzuki Norihiro , Nakahara Jin , Okano Hideyuki 
Published: December 2021

ABSTRACTBackgroundWe previously used an induced pluripotent stem cell-based drug repurposing approach to demonstrate that ropinirole hydrochloride (ropinirole) attenuated amyotrophic lateral sclerosis (ALS)-specific pathological phenotypes. Here, we assessed the safety and feasibility of ropinirole in ALS patients to verify its efficacy.MethodsWe conducted a randomized feasibility trial of ALS. Twenty participants with ALSFRS-R scores greater than 2 points were randomly assigned using dynamic allocation to receive ropinirole or placebo for 24 weeks in the double-blind period. Upon completion, participants could choose to participate in the following 24-week open-label active extension period. The primary outcomes were safety and tolerability. The secondary outcomes for the feasibility trial objective were the change in the ALS Functional Rating Scale-Revised (ALSFRS-R) score, composite functional endpoint, combined assessment of function and survival, event-free survival, and time to ≤50% forced vital capacity (blinded outcome assessment). This study is registered with the UMIN Clinical Trials Registry, UMIN000034954.FindingsTwenty-one participants were randomized into two groups (ropinirole group; n=14) and received ropinirole (n=13) or placebo (n=7) and the data of all participants were analysed using mixed-effects models for repeated measures together. Overall, the incidences of adverse events, most of which had been reported previously, were similar within both groups. Notably, the incidence of gastrointestinal disorders (mainly, temporary mild nausea and diarrhoea) was high at 76·9% in the ropinirole group (14·3% in the placebo group). Regarding the feasibility of verifying efficacy, there were no significant differences in the ALSFRS-R score and combined assessment of function and survival scores during the double-blind period for 6 months, while the participants in the ropinirole group had lived an additional 27·9 weeks without disease progression events compared with the placebo group (log-rank test, 95% confidence interval, 4·3–37·4) at 12 months (secondary outcome).InterpretationRopinirole is safe and tolerable for patients with ALS and this trial indicates feasibility for a subsequent large-scale trial.FundingThis study was funded by The Japan Agency for Medical Research and Development and K Pharma Inc.
Association of regional Covid-19 mortality with indicators of indoor ventilation, including temperature and wind: insights into the upcoming winter
Authors: Leffler Christopher T. , Lykins V Joseph D. , Fram Brandon I. , Yang Edward 
Published: December 2021

AbstractBackgroundOutdoor environmental variables, such as cold temperatures and low wind speed, have been correlated with incidence and mortality from Covid-19 (caused by the SARS-CoV-2 virus). However, as Covid-19 predominantly spreads indoors, the degree to which outdoor environmental variables might directly cause disease spread is unclear.MethodsWorld regions were considered to have reliable data if the excess mortality did not greatly exceed reported Covid-19 mortality. The relative risk of Covid-19 mortality for 142 regions as a function of median weekly temperature and wind speed was determined. For instance, Covid-19 mortality following warm weeks in a country was compared with mortality following cold weeks in the same country.ResultsCovid-19 mortality increases with cooling from 20 C to close to freezing (0 to 4 C, p<0.001). The relation of Covid-19 mortality with temperature demonstrates a maximum close to freezing. Below -5 C, the decrease in mortality with further cooling was statistically significant (p<0.01). With warming above room temperature (20 to 24 C), there is a nonsignificant trend for mortality to increase again. A literature review demonstrated that window opening and indoor ventilation tend to increase with warming in the range from freezing to room temperature.ConclusionThe steep decline in Covid-19 mortality with warming in the range from freezing to room temperature may relate to window opening and less indoor crowding when it is comfortable outside. Below freezing, all windows are closed, and further cooling increases stack ventilation (secondary to indoor-outdoor temperature differences) and thereby tends to decrease Covid-19 mortality. Opening windows and other tools for improving indoor ventilation may decrease the spread of Covid-19.
Is sobriety from alcohol necessary for evaluation of patients presenting with suicidal ideation?
Authors: Keyes Daniel , Hardin Blake , Moore Brandon 
Published: December 2021

BackgroundIt is commonly assumed that patients intoxicated with alcohol are unreliable with respect to their statements of suicidal intent, however no prior literature evaluates the impact of sobriety on suicidal ideation (SI). In typical emergency department (ED) settings, a common practice is to wait until intoxicated suicidal individuals have reached a legally sober limit (ethanol level less than 80 mg/dL) to evaluate safety. We are not aware of any study that establishes the diagnostic reliability of the clinical suicidal ideation evaluation as a function of alcohol intoxication.MethodsThis study is a retrospective review of medical records for patients evaluated in a pre-COVID Midwestern ED for one calendar year. Cases were generated for review based on criteria of having a Psychiatric SW (Social Work) consult and blood alcohol level drawn while in the ED on every Wednesday and Friday of 2017 which produced 1084 cases for review. Chi-square analysis was used for comparison of variables of suicidal ideation with or without alcohol intoxication as defined by blood alcohol level (BAL) ≥80 mg/dL.ResultsIn reference to our initial hypothesis, patients presenting with suicidal ideation and concurrent alcohol intoxication were no longer reporting suicidal ideation at sobriety in 69% of cases, compared to 38% for patients without alcohol levels on presentation. Chi-square analysis demonstrated p=0.000012.ConclusionThe goal of the present study was to demonstrate, with empirical data, a relationship between alcohol intoxication and suicidal ideation. Our data suggests that patients presenting to the ED with complaints related to suicidal behavior who are found to have concurrent alcohol intoxication are more likely to deny suicidal ideation when sober than patients with similar presenting complaints and no alcohol intoxication.
Association of inferior division MCA stroke location with populations with atrial fibrillation incidence
Authors: Kim Ganghyun , Vitti Emilia , Stockbridge Melissa D. , Hillis Argye E. , Faria Andreia V. 
Published: December 2021

ABSTRACTBackground and AimAnatomical features of Middle Cerebral Artery (MCA) bifurcation favors larger emboli entering the inferior rather than superior division. As cardiac source emboli are on average larger than arterial source emboli, we hypothesize that patients with atrial fibrillation have infarcts that involve more temporal and parietal lobes than frontal lobes.MethodsFrom 1,849 patients admitted with evidence of acute or early subacute ischemic stroke on diffusion-weighted MRI (DWI), 482 affected exclusively the “lobar” MCA (sparing the lenticulostriates). They were classified as “frontal predominant” (n=105) or “temporoparietal predominant” (n=197) if at least 75% of the infarct affected the frontal lobe or the temporal and parietal lobes, respectively. Differences between stroke location (frontal or temporoparietal), sex, and race were analyzed by Chi-square test. Results: Men were more likely than women, and white people were more likely than black people to have temporoparietal strokes versus frontal strokes. Patients with confirmed diagnosis of atrial fibrillation have more temporoparietal strokes, compared to frontal strokes.ConclusionMCA ischemic strokes occur more often in temporoparietal areas in men and in white patients, populations with known elevated incidence of atrial fibrillation. Patients with confirmed diagnosis of atrial fibrillation have more temporoparietal strokes, compared to frontal strokes. Results align with the hypothesis that large emboli (mostly from cardiac source) are more likely to cause temporoparietal strokes in the MCA territory, compared to frontal strokes. This association can help guide search for the most likely etiology of infarcts.
Neuron-like function of the nephron central command
Authors: Gyarmati Georgina , Shroff Urvi Nikhil , Riquier-Brison Anne , Stocker Sean D. , Izuhara Audrey , Deepak Sachin , Chen Yibu , Biemesderfer Daniel , James Aaron W. , Minichiello Liliana , Zlokovic Berislav V. , Peti-Peterdi Janos 
Published: December 2021

SUMMARYInteroceptive neurons that sense and regulate our internal milieu have been identified in several organs except in the kidney cortex despite its major importance in maintaining body homeostasis. Here we report that the chief kidney cell type of the macula densa (MD) forms coordinated neural networks in each nephron that resemble peripheral ganglia. A combined in vivo single-cell 4D physiology (sc4DP) and scRNA sequencing approach identified the MD mechanisms of neuronal differentiation, heterogeneity (pacemaker MD cells), sensing of the local and systemic environment via multi-organ crosstalk, and regulation of organ functions by acting as the nephron central command. Consistent with their neuron-like nature, MD cells express the molecular fingerprint of neurodegeneration. Here we put forth the single-cell MD model and concept of local neural networks that control organ and body functions via interoception in normal physiological state and use an integrated mechanism of neurodegeneration in disease.
Distinct within-host bacterial populations ensure function, colonization and transmission in leaf symbiosis
Authors: Acar Tessa , Moreau Sandra , Coen Olivier , De Meyer Frédéric , Leroux Olivier , Beaumel Marine , Wilkin Paul , Carlier Aurélien 
Published: December 2021

AbstractHereditary symbioses have the potential to drive transgenerational effects, yet the mechanisms responsible for transmission of heritable plant symbionts are still poorly understood. The leaf symbiosis betweenDioscorea sansibarensisand the bacteriumOrrella dioscoreaeoffers an appealing model system to study how heritable bacteria are transmitted to the next generation. Here, we demonstrate that inoculation of apical buds with a bacterial suspension is sufficient to colonize newly-formed leaves and propagules, and to ensure transmission to the next plant generation. Flagellar motility is not required for movement inside the plant, but is important for the colonization of new hosts. Further, stringent tissue-specific regulation of putative symbiotic functions highlight the presence of two distinct subpopulations of bacteria in the leaf gland and at the shoot meristem. We propose that bacteria in the leaf gland dedicate resources to symbiotic functions, while dividing bacteria in the shoot tip ensure successful colonization of meristematic tissue, glands and propagules. Compartmentalization of intra-host populations, together with tissue-specific regulation may serve as a robust mechanism for the maintenance of mutualism in leaf symbiosis.ImportanceSeveral plant species form associations with bacteria in their leaves, called leaf symbiosis. These associations are highly specific, but the mechanisms responsible for symbiont transmission are poorly understood. Using the association between the yam speciesDioscorea sansibarensisandOrrella dioscoreaeas a model leaf symbiosis, we provide experimental evidence that bacteria are transmitted vertically and distributed to specific leaf structures via association with shoot meristems. Flagellar motility is required for initial infection, but does not contribute to spread within host tissue. We also provide evidence that bacterial subpopulations at the meristem or in the symbiotic leaf gland differentially express key symbiotic genes. We argue that this separation of functional symbiont populations, coupled to tight control over bacterial infection and transmission, explain the evolutionary robustness of leaf symbiosis. These findings may provide insights into how plants may recruit and maintain beneficial symbionts at the leaf surface.
Blood-based Genomic and Cellular Determinants of Response to Neoadjuvant PD-1 Blockade in Patients with Non-Small-Cell Lung Cancer
Authors: Zhang Xi , Chen Rui , Li Wenqing , Zhang Shengchao , Jiang Mengju , Su Guodong , Liu Yuru , Cai Yu , Huang Wuhao , Xiong Yuyan , Wang Shengguang 
Published: December 2021

AbstractBackgroundDespite the improved survival observed in PD-1/PD-L1 blockade therapy, there still is a lack of response to the anti-PD1 therapy for a large proportion of cancer patients across multiple indications, including non-small cell lung cancer (NSCLC)MethodsTranscriptomic profiling was performed on 57 whole blood samples from 31 NSCLC patients and 5 healthy donors, including both responders and non-responders received anti-PD-1 Tislelizumab plus chemotherapy, to characterize differentially expressed genes (DEGs), signature pathways, and immune cell subsets regulated during treatment. Mutations of oncogenic drivers were identified and associated with therapeutic outcomes in a validation cohort with 1661 cancer patients. These multi-level biomarkers were validated and compared across different methods, external datasets and multiple computational tools.ResultsNSCLC patients examined and achieved pathological complete response (pCR) were considered as responders or non-responders otherwise. Expression of hundreds DEGs (FDR p<0.05, fold change<-2 or >2) was changed in blood during neoadjuvant anti-PD-1 treatment, as well as in lung cancer tissue as compared to normal samples. Enriched PD-1-mediated pathways and elevated cell abundances of CD8 T cells and regulatory T cells were exclusively observed in responder blood samples. In an independent validation cohort of 1661 pan-cancer patients, a panel of 4 top ranked genetic alterations (PTCH1, DNMT3A, PTPRS, JAK2) identified from responders in discovery cohort were found positively associated with the overall survival (p<0.05).ConclusionThese findings suggest peripheral blood-based biomarkers and cell subsets could be utilized to define the response to neoadjuvant PD-1 blockade in NSCLC patients and a set of novel gene mutations is strongly associated with the therapeutic outcome of cancer immunotherapy.
Cell cycle arrest explained the observed bulk 3D genomic alterations in response to long term heat shock for mammalian cells
Authors: Xu Bingxiang , Gao Xiaomeng , Li Xiaoli , Jia Yan , Li Feifei , Zhang Zhihua 
Published: December 2021

AbstractHeat shock is a common environmental stress, while the response of the nucleus to it remains controversial in mammalian cells. Acute reaction and chronic adaptation to environmental stress may have distinct internal rewiring in the gene regulation networks. However, this difference remains largely unexplored. Here, we report that chromatin conformation and chromatin accessibility respond differently in short- and long-term heat shock in human K562 cells. Interestingly, we found that chromatin conformation in K562 cells was largely stable in response to short heat shock, while showed clear and characteristic changes after long-term heat treatment with little alteration in chromatin accessibility during the whole process. We further showed in silico and experimental evidence strongly suggesting that changes in chromatin conformation may largely stem from an accumulation of cells in the M stage of cell cycle in response to heat shock. Our results represent a paradigm shift away from the controversial view of chromatin response to heat shock and emphasize the necessity of cell cycle analysis while when interpreting bulk Hi-C data.