bluuebunny/crossref_metadata_2025 huggingface dataset:
The Clinical Response of Upadacitinib and Risankizumab Is Associated With Reduced Inflammatory Bowel Disease Anti-TNF-α Inadequate Response Mechanisms
Authors: Wang Jing , Macoritto Michael , Guay Heath , Davis Justin W , Levesque Marc C , Cao Xiaohong
Published: December 2022

Background

Janus kinase (JAK) 1 inhibitor upadacitinib and IL-23 inhibitor risankizumab are efficacious in inflammatory bowel disease (IBD) patients who are antitumor necrosis factor (anti-TNF)-α inadequate responders (TNF-IRs). We aimed to understand the mechanisms mediating the response of upadacitinib and risankizumab.

Methods

Eight tissue transcriptomic data sets from IBD patients treated with anti-TNF-α therapies along with single-cell RNAseq data from ulcerative colitis were integrated to identify TNF-IR mechanisms. The RNAseq colon tissue data from clinical studies of TNF-IR Crohn’s disease patients treated with upadacitinib or risankizumab were used to identify TNF-IR mechanisms that were favorably modified by upadacitinib and risankizumab.

Results

We found 7 TNF-IR upregulated modules related to innate/adaptive immune responses, interferon signaling, and tissue remodeling and 6 TNF-IR upregulated cell types related to inflammatory fibroblasts, postcapillary venules, inflammatory monocytes, macrophages, dendritic cells, and cycling B cells. Upadacitinib was associated with a significant decrease in the expression of most TNF-IR upregulated modules in JAK1 responders (JAK1-R); in contrast, there was no change in these modules among TNF-IR patients treated with a placebo or among JAK1 inadequate responders (JAK1-IR). In addition, 4 of the 6 TNF-IR upregulated cell types were significantly decreased after upadacitinib treatment in JAK1-R but not among subjects treated with a placebo or among JAK1-IR patients. We observed similar findings from colon biopsy samples from TNF-IR patients treated with risankizumab.

Conclusions

Collectively, these data suggest that upadacitinib and risankizumab affect TNF-IR upregulated mechanisms, which may account for their clinical response among TNF-IR IBD patients.
Development and Validation of a GC–MS-EI Method to Determine α-PHP in Blood: Application to Samples Collected during Medico-Legal Autopsies
Authors: Machado Francisca , Franco João , Vieira Duarte Nuno , Margalho Cláudia
Published: December 2022

New psychoactive substances (NPSs) still represent an issue of great concern worldwide despite efforts made by national and international control systems to limit the spread of these substances. Alpha-pyrrolidinohexanophenone (α-PHP) is a fairly recent synthetic cathinone (the second largest group of monitored substances in Europe) with only a few published studies on the substance. Though there is a low incidence of NPS consumption in Portugal, a recent increase in apprehensions and detections in biological matrices of the substance was verified. An analytical methodology was developed and validated for determining and quantitating α-PHP in blood. Solid-phase extraction was employed for sample preparation (500 μL), which was further analyzed by gas chromatography--mass spectrometry-electron ionization in single-ion monitoring mode with cocaine-d3 as the internal standard. Method validation followed the guidelines of the American National Standards Institute/AAFS Standards Board (ANSI/ASB Standard 036). The procedure was linear between 10 and 1,000 ng/mL, with determination coefficients (r2) higher than 0.999. Carryover was not observed. A limit of detection of 5 ng/mL and a limit of quantitation of 10 ng/mL were achieved. Intraday and intermediate precision and bias assessment showed satisfactory results (coefficient of variation <17.7%; bias <11.6%), and extraction efficiency ranged from 98.5% to 103.3%. The stability of the substance was considered acceptable for at least 6 h at room temperature, 48 h in the autosampler and 21 days after five freeze/thaw cycles. The developed methodology was applied to 15 real samples from the Laboratory of Chemistry and Forensic Toxicology, Centre Branch of the National Institute of Legal Medicine and Forensic Sciences, Portugal, with drug concentrations ranging from 15 to 227 ng/mL. Available information for each case is also detailed in the present article.
Potential Management Options for the Invasive Moth Spodoptera frugiperda in Europe
Authors: Babendreier Dirk , Toepfer Stefan , Bateman Melanie , Kenis Marc
Published: December 2022

We here review and discuss management options that growers in Europe could take in response to the expected invasion of the fall armyworm, Spodoptera frugiperda (Lepidoptera: Noctuidae). The focus is put on maize but the information provided is also relevant for other crops potentially affected. A sound forecasting system for fall armyworm both on a regional as well as at local scale should be established to alert growers as early as possible. Whilst a number of cultural control methods are adopted by maize growers in different regions globally to fight fall armyworm, many of them may either not be highly effective, too laborious, or otherwise unfeasible within the mechanized crop production systems used in Europe. Potential is seen in the stimulation of natural enemies through conservation biocontrol approaches, e.g., the planting of flower strips or intermediate cover crops, reducing tillage intensity, and avoiding broad-spectrum insecticides. To manage fall armyworm infestations, several effective biologically-based products are available globally, and some in Europe, e.g., based on specific baculoviruses, certain Bacillus thuringiensis strains, few entomopathogenic nematodes, and a number of botanicals. These should be given priority to avoid a major influx of insecticides into the maize agro-ecosystem once the fall armyworm arrives and in case growers are not prepared. Plant protection companies, particularly biocontrol companies should act proactively in starting registration of ingredients and products against fall armyworm in Europe. European maize growers should be made aware, in time, of key features of this new invasive pest and appropriate control options.
Low Impact of Fall Armyworm (Spodoptera frugiperda Smith) (Lepidoptera: Noctuidae) Across Smallholder Fields in Malawi and Zambia
Authors: Harrison Rhett , Banda John , Chipabika Gilson , Chisonga Chipo , Katema Christopher , Mabote Ndalamei Damian , Nyirenda Stephen , Tembo Howard
Published: December 2022

Fall armyworm (Spodoptera frugiperda Smith), a serious pest of cereals from the Americas, has spread across sub-Saharan Africa and Asia since 2016, threatening the food security and incomes of millions of smallholder farmers. To measure the impact of S. frugiperda under different management approaches, we established on-farm trials across 12 landscapes (615−1,379 mm mean annual rainfall) in Malawi and Zambia during the 2019/2020 and 2020/2021 seasons. Here we present the results from our conventional tillage, monocrop maize, no pesticide treatment, which served to monitor the background S. frugiperda impact in the absence of control measures. Median plot-level S. frugiperda incidence ranged between 0.00 and 0.52 across landscapes. Considering severe leaf damage (Davis score ≥5), the proportion of affected plants varied between 0.00 and 0.30 at the plot scale, but only 3% of plots had ≥10% severely damaged plants. While incidence and damage severity varied substantially among sites and seasons, our models indicate that they were lower in high tree cover landscapes, in the late season scouting, and in the 2020/2021 season. Yield could not be predicted from S. frugiperda incidence or leaf damage. Our results suggest S. frugiperda impacts may have been overestimated at many sites across sub-Saharan Africa. S. frugiperda incidence and damage declined through the cropping season, indicating that natural mortality factors were limiting populations, and none of our plots were heavily impacted. Long-term S. frugiperda management should be based on Integrated Pest Management (IPM) principles, including minimising the use of chemical pesticides to protect natural enemies.
Factors Associated With Neuromusculoskeletal Injury and Disability in Navy and Marine Corps Personnel
Authors: Fraser John J , MacGregor Andrew J , Fechner Kenneth M , Galarneau Michael R
Published: December 2022

Introduction

Neuromusculoskeletal injuries (NMSKI) are very common in the military, which contribute to short- and long-term disability.

Materials and Methods

Population-level NMSKI, limited duty (LIMDU), and long-term disability episode counts in the U.S. Navy (USN) and U.S. Marine Corps (USMC) from December 2016 to August 2021 were extracted from the Musculoskeletal Naval Epidemiological Surveillance Tool. The incidence of NMSKI, LIMDU, and long-term disability was calculated. A hurdle negative binomial regression evaluated the association of body region, sex, age, rank, age by rank, and service branch on NMSKI, LIMDU, and long-term disability incidence.

Results

From December 2016 to August 2021, there were 2,004,196 NMSKI episodes (USN: 3,285/1,000 Sailors; USMC: 4,418/1,000 Marines), 16,791 LIMDU episodes (USN: 32/1,000 Sailors; USMC: 29/1,000 Marines), and 2,783 long-term disability episodes (USN: 5/1,000 Sailors; USMC: 5/1,000 Marines). There was a large-magnitude protective effect on NMSKI during the pandemic (relative risk, USN: 0.70; USMC: 0.75). Low back and ankle-foot were the most common, primarily affecting female personnel, aged 25-44 years, senior enlisted, in the USMC. Shoulder, arm, pelvis-hip, and knee conditions had the greatest rates of disability, with female sex, enlisted ranks, aged 18-24 years, and service in the USMC having the most salient risk factors.

Conclusion

Body region, sex, age, rank, and branch were the salient factors for NMSKI. The significant protective effect during the pandemic was likely a function of reduced physical exposure and limited access to nonurgent care. Geographically accessible specialized care, aligned with communities with the greatest risk, is needed for timely NMSKI prevention, assessment, and treatment.
Evaluation of neurological testing for hand–arm vibration syndrome
Authors: Ahmad S , House R , Holness D L , Nisenbaum R , Thompson A M S
Published: December 2022

Background

The neurological component of hand–arm vibration syndrome (HAVS) uses the Stockholm Workshop Scale sensorineural (SWS SN) stages for classification. Proximal compressive neuropathies are common in HAVS and the symptoms are similar to SN HAVS. The SWS may not be a valid staging tool if a patient has comorbid proximal compression neuropathy.

Aims

To evaluate the prevalence of proximal compression neuropathy in patients presenting for HAVS assessment and examine the association between compressive neuropathies and SWS SN.

Methods

A standardized assessment protocol was used to assess 431 patients for HAVS at St. Michael’s Hospital, Toronto, Ontario. The prevalence of median and ulnar compressive neuropathies was determined. The association between proximal compression neuropathies and SWS SN stage (0/1 versus 2/3) was evaluated using Chi-square and Fisher’s exact tests as well as multivariable logistic regression.

Results

Most patients (79%) reported numbness and 20% had reduced sensory perception (SWS SN Stage 2/3). Almost half (45%) had median neuropathy at the wrist and 7% had ulnar neuropathy. There was no association between the SWS SN stage and median or ulnar neuropathy.

Conclusions

Two neurological lesions should be investigated in patients presenting for HAVS assessment: compressive neuropathy and digital neuropathy. The prevalence of compressive neuropathies is high in patients being assessed for HAVS and therefore nerve conduction studies (NCS) should be included in HAVS assessment protocols. Comorbid proximal neuropathy does not affect the SWS SN stage; therefore, NCS and SWS SN seem to be measuring different neurological outcomes in HAVS patients.
X-ray and optical spectroscopic study of a γ Cassiopeiae analog source π Aquarii
Authors: Tsujimoto Masahiro , Hayashi Takayuki , Morihana Kumiko , Moritani Yuki
Published: December 2022

γ Cas analog sources are a subset of Be stars that emit intense and hard X-ray emission. Two competing ideas for their X-ray production mechanism are (a) the magnetic activities of the Be star and its disk and (b) the accretion from the Be star to an unidentified compact object. Among such sources, π Aqr plays a pivotal role as it is one of the only two spectroscopic binaries observed for many orbital cycles and one of the three sources with X-ray brightness sufficient for detailed X-ray spectroscopy. Bjorkman et al. (2002, ApJ, 573, 812) estimated the secondary mass >2.0 M⊙ with optical spectroscopy, which would argue against the compact object being a white dwarf (WD). However, their dynamical mass solution is inconsistent with an evolutionary solution and their radial velocity measurement is inconsistent with later work by Nazé et al. (2019, A&A, 632, A23). We revisit this issue by adding a new data set with the NuSTAR X-ray observatory and the HIDES échelle spectrograph. We found that the radial velocity amplitude is consistent with Nazé et al. (2019, A&A, 632, A23), which is only half of that claimed by Bjorkman et al. (2002, ApJ, 573, 812). Fixing the radial velocity amplitude of the primary, the secondary mass is estimated as <1.4 M⊙ over an assumed range of the primary mass and the inclination angle. We further constrained the inclination angle and the secondary mass independently by fitting the X-ray spectra with a non-magnetic or magnetic accreting WD model under the assumption that the secondary is indeed a WD. The two results match well. We thus argue that the possibility of the secondary being a WD should not be excluded for π Aqr.
Cell-type-specific alternative splicing in the Arabidopsis germline
Authors: Misra Chandra Shekhar , Sousa António G G , Barros Pedro M , Kermanov Anton , Becker Jörg D
Published: December 2022

During sexual reproduction in flowering plants, the two haploid sperm cells (SCs) embedded within the cytoplasm of a growing pollen tube are carried to the embryo sac for double fertilization. Pollen development in flowering plants is a dynamic process that encompasses changes at transcriptome and epigenome levels. While the transcriptome of pollen and SCs in Arabidopsis (Arabidopsis thaliana) is well documented, previous analyses have mostly been based on gene-level expression. In-depth transcriptome analysis, particularly the extent of alternative splicing (AS) at the resolution of SC and vegetative nucleus (VN), is still lacking. Therefore, we performed RNA-seq analysis to generate a spliceome map of Arabidopsis SCs and VN isolated from mature pollen grains. Based on our de novo transcriptome assembly, we identified 58,039 transcripts, including 9,681 novel transcripts, of which 2,091 were expressed in SCs and 3,600 in VN. Four hundred and sixty-eight genes were regulated both at gene and splicing levels, with many having functions in mRNA splicing, chromatin modification, and protein localization. Moreover, a comparison with egg cell RNA-seq data uncovered sex-specific regulation of transcription and splicing factors. Our study provides insights into a gamete-specific AS landscape at unprecedented resolution.
Algal PETC-Pro171-Leu suppresses electron transfer in cytochromeb6funder acidic lumenal conditions
Authors: Ozawa Shin-Ichiro , Buchert Felix , Reuys Ruby , Hippler Michael , Takahashi Yuichiro
Published: December 2022

Linear photosynthetic electron flow (LEF) produces NADPH and generates a proton electrochemical potential gradient across the thylakoid membrane to synthesize ATP, both of which are required for CO2 fixation. As cellular demand for ATP and NADPH varies, cyclic electron flow (CEF) between Photosystem I and the cytochrome b6f complex (b6f) produces extra ATP. b6f regulates LEF and CEF via photosynthetic control, which is a pH-dependent b6f slowdown of plastoquinol oxidation at the lumenal site. This protection mechanism is triggered at more alkaline lumen pH in the pgr1 (proton gradient regulation 1) mutant of the vascular plant Arabidopsis (Arabidopsis thaliana), which contains a Pro194Leu substitution in the b6f Rieske Iron-sulfur protein Photosynthetic Electron Transfer C (PETC) subunit. In this work, we introduced the equivalent pgr1 mutation in the green alga Chlamydomonas reinhardtii to generate PETC-P171L. Consistent with the pgr1 phenotype, PETC-P171L displayed impaired NPQ induction along with slower photoautotrophic growth under high light conditions. Our data provide evidence that the ΔpH component in PETC-P171L depends on oxygen availability. Only under low oxygen conditions was the ΔpH component sufficient to trigger a phenotype in algal PETC-P171L where the mutant b6f was more restricted to oxidize the plastoquinol pool and showed diminished electron flow through the b6f complex. These results demonstrate that photosynthetic control of different stringency are established in C. reinhardtii depending on the cellular metabolism, and the lumen pH-sensitive PETC-P171L was generated to read out various associated effects.
Clinically Relevant Decreases in Neck/Shoulder Pain Among Office Workers Are Associated With Strength Training Adherence and Exercise Compliance: Explorative Analyses From a Randomized Controlled Trial
Authors: Dalager Tina , Welch Alyssa , O’Leary Shaun Patrick , Johnston Venerina , Sjøgaard Gisela
Published: December 2022

Objective

The objectives of this study were to quantify training adherence and exercise compliance during a workplace-based strength training intervention delivered to office workers over a 12-week period and to analyze the association with clinically relevant pain reductions.

Methods

A subsample of 269 participants completed a training diary from which measures of training adherence and exercise compliance (training volume, load, and progression) were calculated. The intervention consisted of 5 specific exercises targeting the neck/shoulder area (neck, shoulders, and upper back). The associations of training adherence, quitting time, and measures of exercise compliance with 3-month pain intensity (on a scale from 0 to 9) were analyzed for the whole sample, pain cases (reporting pain of ≥3 at baseline), participants attaining/not attaining clinically relevant pain reductions (≥30%), and participants meeting/not meeting per-protocol training adherence of ≥70%.

Results

Participants reported reduced pain in the neck/shoulder area after 12 weeks of specific strength training, especially women and pain cases, with the caveat that attaining clinically relevant pain reductions depended on the levels of training adherence and exercise compliance attained. Over the 12-week intervention, 30% of the participants were absent for a minimum of 2 consecutive weeks (quitting time), with the median quitting time at approximately weeks 6 to 8. With a threshold of 70% training adherence, a total training volume of approximately 11,000 kg (only in women) and progressions of 1 to 2 times baseline values were shown to be significant for clinically relevant pain reductions.

Conclusion

Strength training produced clinically relevant reductions in neck/shoulder pain when appropriate levels of training adherence and exercise compliance were attained. This finding was particularly evident for women and pain cases. We advocate for the inclusion of both training adherence and exercise compliance measures in future studies. To optimize intervention benefits, motivational activities after 6 weeks are needed to avoid participants quitting.

Impact

These data can be used to design and prescribe clinically relevant rehabilitation pain programs and interventions.
Speech Illusions in People at Clinical High Risk for Psychosis Linked to Clinical Outcome
Authors: Hird Emily J , Ohmuro Noriyuki , Allen Paul , Moseley Peter , Kempton Matthew J , Modinos Gemma , Sachs Gabriele , van der Gaag Mark , de Haan Lieuwe , Gadelha Ary , Bressan Rodrigo , Barrantes-Vidal Neus , Ruhrmann Stephan , Catalan Ana ,   EU-GEI High Risk Study, McGuire Philip , Valmaggia Lucia R , Kempton Matthew J , Calem Maria , Tognin Stefania , Modinos Gemma , de Haan Lieuwe , van der Gaag Mark , Velthorst Eva , Kraan Tamar C , van Dam Daniella S , Burger Nadine , Nelson Barnaby , McGorry Patrick , Paul Amminger Günter , Pantelis Christos , Politis Athena , Goodall Joanne , Riecher-Rössler Anita , Borgwardt Stefan , Rapp Charlotte , Ittig Sarah , Studerus Erich , Smieskova Renata , Bressan Rodrigo , Gadelha Ary , Brietzke Elisa , Asevedo Graccielle , Asevedo Elson , Zugman Andre , Barrantes-Vidal Neus , Domínguez-Martínez Tecelli , Torrecilla Pilar , Kwapil Thomas R , Monsonet Manel , Hinojosa Lídia , Kazes Mathilde , Daban Claire , Bourgin Julie , Gay Olivier , Mam-Lam-Fook Célia , Krebs Marie-Odile , Nordholm Dorte , Randers Lasse , Krakauer Kristine , Glenthøj Louise , Glenthøj Birte , Nordentoft Merete , Ruhrmann Stephan , Gebhard Dominika , Arnhold Julia , Klosterkötter Joachim , Sachs Gabriele , Lasser Iris , Winklbaur Bernadette , Delespaul Philippe A , Rutten Bart P , van Os1 Jim , McGuire Philip
Published: December 2022

Background and hypothesis

Around 20% of people at clinical high risk (CHR) for psychosis later develop a psychotic disorder, but it is difficult to predict who this will be. We assessed the incidence of hearing speech (termed speech illusions [SIs]) in noise in CHR participants and examined whether this was associated with adverse clinical outcomes.

Study design

At baseline, 344 CHR participants and 67 healthy controls were presented with a computerized white noise task and asked whether they heard speech, and whether speech was neutral, affective, or whether they were uncertain about its valence. After 2 years, we assessed whether participants transitioned to psychosis, or remitted from the CHR state, and their functioning.

Study results

CHR participants had a lower sensitivity to the task. Logistic regression revealed that a bias towards hearing targets in stimuli was associated with remission status (OR = 0.21, P = 042). Conversely, hearing SIs with uncertain valence at baseline was associated with reduced likelihood of remission (OR = 7.72. P = .007). When we assessed only participants who did not take antipsychotic medication at baseline, the association between hearing SIs with uncertain valence at baseline and remission likelihood remained (OR = 7.61, P = .043) and this variable was additionally associated with a greater likelihood of transition to psychosis (OR = 5.34, P = .029).

Conclusions

In CHR individuals, a tendency to hear speech in noise, and uncertainty about the affective valence of this speech, is associated with adverse outcomes. This task could be used in a battery of cognitive markers to stratify CHR participants according to subsequent outcomes.
Belief Updating in Subclinical and Clinical Delusions
Authors: Fromm Sophie , Katthagen Teresa , Deserno Lorenz , Heinz Andreas , Kaminski Jakob , Schlagenhauf Florian
Published: December 2022

Background and Hypothesis

Current frameworks propose that delusions result from aberrant belief updating due to altered prediction error (PE) signaling and misestimation of environmental volatility. We aimed to investigate whether behavioral and neural signatures of belief updating are specifically related to the presence of delusions or generally associated with manifest schizophrenia.

Methods

Our cross-sectional design includes human participants (n[female/male] = 66[25/41]), stratified into four groups: healthy participants with minimal (n = 22) or strong delusional-like ideation (n = 18), and participants with diagnosed schizophrenia with minimal (n = 13) or strong delusions (n = 13), resulting in a 2 × 2 design, which allows to test for the effects of delusion and diagnosis. Participants performed a reversal learning task with stable and volatile task contingencies during fMRI scanning. We formalized learning with a hierarchical Gaussian filter model and conducted model-based fMRI analysis regarding beliefs of outcome uncertainty and volatility, precision-weighted PEs of the outcome- and the volatility-belief.

Results

Patients with schizophrenia as compared to healthy controls showed lower accuracy and heightened choice switching, while delusional ideation did not affect these measures. Participants with delusions showed increased precision-weighted PE-related neural activation in fronto-striatal regions. People with diagnosed schizophrenia overestimated environmental volatility and showed an attenuated neural representation of volatility in the anterior insula, medial frontal and angular gyrus.

Conclusions

Delusional beliefs are associated with altered striatal PE-signals. Juxtaposing, the potentially unsettling belief that the environment is constantly changing and weaker neural encoding of this subjective volatility seems to be associated with manifest schizophrenia, but not with the presence of delusional ideation.
Activity of GABA neurons in the zona incerta and ventral lateral periaqueductal grey is biased towards sleep
Authors: Blanco-Centurion Carlos , Vidal-Ortiz Aurelio , Sato Takashi , Shiromani Priyattam J
Published: December 2022

Study Objectives

As in various brain regions the activity of gamma-aminobutyric acid (GABA) neurons is largely unknown, we measured in vivo changes in calcium fluorescence in GABA neurons in the zona incerta (ZI) and the ventral lateral periaqueductal grey (vlPAG), two areas that have been implicated in regulating sleep.

Methods

vGAT-Cre mice were implanted with sleep electrodes, microinjected with rAAV-DIO-GCaMP6 into the ZI (n = 6) or vlPAG (n = 5) (isoflurane anesthesia) and a GRIN (Gradient-Index) lens inserted atop the injection site. Twenty-one days later, fluorescence in individual vGAT neurons was recorded over multiple REM cycles. Regions of interest corresponding to individual vGAT somata were automatically extracted with PCA–ICA analysis.

Results

In the ZI, 372 neurons were identified. Previously, we had recorded the activity of 310 vGAT neurons in the ZI and we combined the published dataset with the new dataset to create a comprehensive dataset of ZI vGAT neurons (total neurons = 682; mice = 11). In the vlPAG, 169 neurons (mice = 5) were identified. In both regions, most neurons were maximally active in REM sleep (R-Max; ZI = 51.0%, vlPAG = 60.9%). The second most abundant group was W-Max (ZI = 23.9%, vlPAG = 25.4%). In the ZI, but not in vlPAG, there were neurons that were NREMS-Max (11.7%). vlPAG had REMS-Off neurons (8.3%). In both areas, there were two minor classes: wake/REMS-Max and state indifferent. In the ZI, the NREMS-Max neurons fluoresced 30 s ahead of sleep onset.

Conclusions

These descriptive data show that the activity of GABA neurons is biased in favor of sleep in two brain regions implicated in sleep.
Manganese-induced neuronal apoptosis: new insights into the role of endoplasmic reticulum stress in regulating autophagy-related proteins
Authors: Liu Chang , Ju Rong
Published: December 2022

Manganese (Mn) is an essential trace element that participates in various physiological and pathological processes. However, epidemiological observations indicate that overexposure to Mn is strongly associated with neurodegenerative disorders and has been recognized as a potential risk factor of neuronal apoptosis. Many mechanisms are involved in the pathogenesis of Mn-induced neuronal apoptosis, such as reactive oxygen species generation, neuroinflammation reactions, protein accumulation, endoplasmic reticulum stress (ER stress), and autophagy, all of which collectively accelerate the process of nerve cell damage. As sophisticated cellular processes for maintaining intracellular homeostasis, ER-mediated unfolded protein response and autophagy both play bilateral roles including cell protection and cell injury under pathophysiological conditions, which might interact with each other. Although emerging evidence suggests that ER stress is involved in regulating the compensatory activation of autophagy to promote cell survival, the inherent relationship between ER stress and autophagy on Mn-induced neurotoxicity remains obscure. Here, our review focuses on discussing the existing mechanisms and connections between ER stress, autophagy, and apoptosis, which provide a new perspective on Mn-induced neuronal apoptosis, and the pathogenesis of neurodegenerative diseases.
Thrombotic Thrombocytopenic Purpura in a Parturient Leading to Life-Threatening Thrombocytopenia and Neonatal Demise—A Case Report
Authors: Berger Amnon A. , Kowalczyk John J. , Hess Philip E. , Li Yunping
Published: December 2022

Thrombocytopenia is common (up to 12%) in pregnancy; thrombotic thrombocytopenia is a rare cause of thrombocytopenia; however, it is immediately life-threatening to both mother and fetus and requires immediate intervention. This is compounded by the need to act on a presumptive diagnosis with high level of suspicion given the relatively long laboratory confirmation time. A 31-year-old gravida 3, para 1 parturient at 26 weeks of gestation presented to outside hospital with recent onset of easy bruising and blurry vision. A blood count was drawn and showed a platelet count of 19,000/μL. She was transferred to our institution for management where an initial diagnosis of preeclampsia with severe features was made based on thrombocytopenia and fetal growth restriction (<1%). Platelet count nadired at 14,000/μL and a blood smear showed schistocytes, suggesting microangiopathic hemolysis, prompting discussion of urgent cesarean delivery and anesthesia consult. An urgent hematology consult led to presumptively diagnosing thrombotic thrombocytopenic purpura and cesarean delivery was deferred after discussion with the patient and team. Plasma exchange and steroid therapy were started promptly, and her platelet count improved within 12 hours. Unfortunately, the patient experienced neonatal demise. Undetectable ADAMTS13 levels confirmed diagnosis of thrombotic thrombocytopenia. She was transitioned to rituximab, platelets recovered to baseline, and she continues to do well. Thrombotic thrombocytopenia is a rare, life-threatening cause of thrombocytopenia in pregnancy. Despite grim fetal prognosis, especially in early pregnancy, low threshold of suspicion, early anesthesia involvement, and multidisciplinary approach can facilitate diagnosis and timely intervention. In our case, it was likely lifesaving.
Dose–response relationship and effect modifier of stabilisation exercises in nonspecific low back pain: a project-wide individual patient data re-analysis on 1483 intervention participants
Authors: Niederer Daniel , Pfeifer Ann-Christin , Engel Tilman , Block Andrea , Schäfer Robin , Floessel Philipp , Beck Heidrun , Platen Petra , Schiltenwolf Marcus , Schneider Christian , Wippert Pia-Maria , Vogt Lutz , Mayer Frank
Published: December 2022

This planned MiSpEx-Network reanalysis was designed to derive a dose–response relationship under consideration of further effect modifiers in exercises on low back pain. One thousand four hundred eighty three intervention participants with low back pain (mean age, 40.9 years [SD 14 years]) performed stabilisation exercises (3 weeks supervised, 9 weeks self-administered). Patients reported pain intensity, disability, and disability days at baseline, 3 weeks, 12 weeks, and 6 months post randomisation. Exercise characteristics and effect modifiers were prospectively monitored. Beyond the comparison to the results of the control group, linear mixed models were calculated to determine a dose–response relationship. The interventions led to small but significantly larger symptom reductions than in the control group at each measurement. Longer durations of the intervention led to larger symptom reductions. Higher exercise frequencies were associated with a decrease in pain intensity: to train once more per week led to a mean decrease of 0.93 points in pain intensity [95% CI = −1.54 to −0.32]. Disability days were also impacted (estimate = −0.07 [−0.14 to 0.00]), but disability was not (−0.09 [−0.67 to 0.48]). Adding perturbation was superior to adding stretching or a behavioural module. The relationships were robust when additional effect modifiers were considered and against the control group' effects. The odds ratio for a clinically important effect with higher exercise frequencies decreased at 3 weeks (OR = 0.71 [0.618-0.813] for >2.5*week−1) and increased at 12 weeks (1.13 [1.006-1.270], >1.5*week−1). Using longer intervention durations, adding a perturbation component to the stabilisation trainings and using higher frequencies (up to a certain point) may lead to an even more beneficial response on exercise in patients with low back pain. Developing strategies to maintain a training frequency of at least 2 times per week may be relevant in stabilisation exercises to treat low back pain.
Inbreeding depression in polyploid species: a meta-analysis
Authors: Clo Josselin , Kolář Filip
Published: December 2022

Whole-genome duplication is a common mutation in eukaryotes with far-reaching phenotypic effects, the resulting morphological and fitness consequences and how they affect the survival of polyploid lineages are intensively studied. Another important factor may also determine the probability of establishment and success of polyploid lineages: inbreeding depression. Inbreeding depression is expected to play an important role in the establishment of neopolyploid lineages, their capacity to colonize new environments, and in the simultaneous evolution of ploidy and other life-history traits such as self-fertilization. Both theoretically and empirically, there is no consensus on the consequences of polyploidy on inbreeding depression. In this meta-analysis, we investigated the effect of polyploidy on the evolution of inbreeding depression, by performing a meta-analysis within angiosperm species. The main results of our study are that the consequences of polyploidy on inbreeding depression are complex and depend on the time since polyploidization. We found that young polyploid lineages have a much lower amount of inbreeding depression than their diploid relatives and their established counterparts. Natural polyploid lineages are intermediate and have a higher amount of inbreeding depression than synthetic neopolyploids, and a smaller amount than diploids, suggesting that the negative effect of polyploidy on inbreeding depression decreases with time since polyploidization.
Replication concerns in sports and exercise science: a narrative review of selected methodological issues in the field
Authors: Mesquida Cristian , Murphy Jennifer , Lakens Daniël , Warne Joe
Published: December 2022

Known methodological issues such as publication bias, questionable research practices and studies with underpowered designs are known to decrease the replicability of study findings. The presence of such issues has been widely established across different research fields, especially in psychology. Their presence raised the first concerns that the replicability of study findings could be low and led researchers to conduct large replication projects. These replication projects revealed that a significant portion of original study findings could not be replicated, giving rise to the conceptualization of the replication crisis. Although previous research in the field of sports and exercise science has identified the first warning signs, such as an overwhelming proportion of significant findings, small sample sizes and lack of data availability, their possible consequences for the replicability of our field have been overlooked. We discuss the consequences of the above issues on the replicability of our field and offer potential solutions to improve replicability.
Is Asian tiger mosquito (Aedes albopictus) going to become homodynamic in Southern Europe in the next decades due to climate change?
Authors: Del Lesto Irene , De Liberato Claudio , Casini Riccardo , Magliano Adele , Ermenegildi Arianna , Romiti Federico
Published: December 2022

The Asian tiger mosquito,Aedes albopictus, competent vector of several arboviruses, poses significant impact on human health worldwide. Although global warming is a driver ofA. albopictusrange expansion, few studies focused on its effects on homodynamicity (i.e. the ability to breed all-year-round), a key factor of vectorial capacity and a primary condition for anAedes-borne disease to become endemic in temperate areas. Data from a 4-year monitoring network set in Central Italy and records from weather stations were used to assess winter adult activity and weekly minimum temperatures. Winter oviposition occurred in 38 localities with a seasonal mean photoperiod of 9.7 : 14.3 (L : D) h. Positive collections (87) occurred with an average minimum temperature of the two and three weeks before sampling of approximately 4°C. According to these evidences and considering the climate projections of three global climate models and three shared socio-economic pathways for the next three 20-year periods (from 2021 to 2080), the minimum temperature of January will increase enough to allow an all-year-round oviposition ofA. albopictusin several areas of the Mediterranean Basin. Due to vector homodynamicity,Aedes-borne diseases could become endemic in Southern Europe by the end of the twenty-first century, worsening the burden on human health.
Compressed hydrogen atoms confined within generic boxes
Authors: Van Gorder Robert A.
Published: December 2022

The ‘compressed hydrogen atom’ problem involves solving the Schrödinger equation for a hydrogen atom confined within an impenetrable (often, spherical) box, with the wave function vanishing on the boundary of this box. To better understand the role the structure of the box plays on the compressed hydrogen atom, we study the compressed hydrogen atom in boxes of myriad shapes and sizes, developing a theory for how the structure of a generic box influences the hydrogen ground state energy. Our theory predicts that the ground state energy increases with the first Dirichlet eigenvalue (which encodes information on both the shape and size of a box) of the box and decreases with the distance of the nucleus from the boundary of the box. This theoretical prediction is supported by numerical simulations and variational approximations. Consideration is also given to the problem of a shell-confined hydrogen atom, with the electron confined to a separate ‘cage’ away from the nucleus. The behaviour of the shell-confined hydrogen ground state is well-approximated by a perturbation theory we develop for generic cages. Our results provide a unified framework for understanding confined, high-pressure hydrogen with relevance to applications ranging from crystal lattices of hydrogen to metallic hydrogen.
Drosophila
olfaction: past, present and future
Authors: Benton Richard
Published: December 2022

Among the many wonders of nature, the sense of smell of the fly
Drosophila melanogaster
might seem, at first glance, of esoteric interest. Nevertheless, for over a century, the ‘nose’ of this insect has been an extraordinary system to explore questions in animal behaviour, ecology and evolution, neuroscience, physiology and molecular genetics. The insights gained are relevant for our understanding of the sensory biology of vertebrates, including humans, and other insect species, encompassing those detrimental to human health. Here, I present an overview of our current knowledge of
D. melanogaster
olfaction, from molecules to behaviours, with an emphasis on the historical motivations of studies and illustration of how technical innovations have enabled advances. I also highlight some of the pressing and long-term questions.
Insights into the evolution of herbivory from a leaf-mining, drosophilid fly
Authors: Aguilar Jessica M. , Gloss Andrew D. , Suzuki Hiromu C. , Verster Kirsten I. , Singhal Malvika , Hoff Jordan , Grebenok Robert , Nabity Paul D. , Behmer Spencer T. , Whiteman Noah K.
Published: December 2022

Herbivorous insects and their host plants comprise most known species on Earth. Illuminating how herbivory repeatedly evolved in insects from non-herbivorous lineages is critical to understanding how this biodiversity is created and maintained. We characterized the trophic niche ofScaptomyza flava, a representative of a lineage nested within theDrosophilathat transitioned to herbivory ∼15 million years ago. We used natural history studies to determine ifS. flavais a true herbivore or a cryptic microbe-feeder. Specifically, we quantified oviposition substrate choice and larval viability across food-types, trophic-related morphological traits, and nitrogen isotope and sterol profiles across putatively herbivorous and non-herbivorous drosophilids. We confirmed thatS. flavais an obligate herbivore of living plants. Paired with its genetic model host,Arabidopsis thaliana, S. flavais a novel and powerful system for exploring mechanisms underlying the evolution of herbivory, a complex trait that enabled the exceptional diversification of insects.
Parasite transmission in size-structured populations
Authors: Shaw Kelsey E , Cloud Rebecca E , Syed Raeyan , Civitello David J
Published: December 2022

Host heterogeneity can impact parasite transmission, but determining underlying traits and incorporating them into transmission models remains challenging. Body size is easily measured and influences numerous ecological interactions, including transmission. In the snail-schistosome system, larger snails have a higher exposure to parasites but lower susceptibility to infection per parasite. We quantified the impact of size-based heterogeneity on population-level transmission by conducting transmission trials in differently size-structured snail populations and competing size-dependent transmission models. Populations with greater proportions of large snails had lower prevalence, and small snails were shielded from infection by co-occurring large conspecifics. Using the winning size-explicit model, we then estimated that schistosome transmission varies dramatically across time due to seasonal changes in snail population size structure. Thus, incorporating traits such as body size, which are impacted by and directly affect host ecology, into transmission models could yield insights for natural dynamics and disease mitigation in many systems.

Open Research Statement

All experimental data and novel code used for data analysis are currently available on Figshare via this private link:https://figshare.com/s/7d70b88220b912e7eec5. Data will be made public on Figshare upon acceptance. Data set utilized for Figure 4 are from the following source: Rumi, A., D. Gutiérrez Gregoric, and A. Roche. 2009. Tendencias Del Crecimiento Individual en Poblaciones Naturales de Biomphalaria spp. (Gastropoda, Planorbidae) en la Cuenca del Plata, Argentina.Comunicaciones de la Sociedad Malacológica del Uruguay. URL:https://www.redalyc.org/articulo.oa?id=52414008002
Increased mRNA expression of CDKN2A is a transcriptomic marker of clinically aggressive meningiomas
Authors: Wang Justin Z. , Patil Vikas , Liu Jeff , Dogin Helin , Behling Felix , Skardelly Marco , Tatagiba Marcos , Hoffman Elgin , Bunda Severa , Yakubov Rebecca , Kaloti Ramneet , Brandner Sebastian , Gao Andrew , Gadol Aaron-Cohen , Barnholtz-Sloan Jennifer , Raleigh David , Sahm Felix , Boutros Paul C. , Tabatabai Ghazaleh , Aldape Kenneth , Nassiri Farshad , Zadeh Gelareh
Published: December 2022

Background

Homozygous loss of CDKN2A/B is a genetic alteration found in many cancer types including meningiomas, where it is associated with poor clinical outcome. It is now also a diagnostic criterion for grade 3 meningiomas in the 2021 WHO classification for central nervous system tumors. However, as in other cancers, the relationship between copy number loss of CDKN2A/B and expression of its gene product is unclear and may be either commensurate or paradoxical in nature. Therefore, we aimed to investigate the association of CDKN2A mRNA expression with clinical prognosis, WHO grade, and other molecular biomarkers in meningiomas such as DNA methylation, molecular group, and proteomics.

Methods

We used multidimensional molecular data of 490 meningioma samples from 4 independent cohorts to examine the relationship between mRNA expression of CDKN2A and copy number status, its correlation to clinical outcome, the transcriptomic pathways altered in differential CDKN2A expression, and its relationship with DNA methylation, and proteomics using an integrated molecular approach.

Results

Meningiomas without any copy number loss were dichotomized into high (CDKN2Ahigh) and low (CDKN2Alow) CDKN2A mRNA expression groups. Patients with CDKN2Ahighmeningiomas had poorer progression free survival (PFS) compared to those with CDKN2Alowmeningiomas. CDKN2A mRNA expression was increased in more aggressive molecular groups, and in higher WHO grade meningiomas across all cohorts. CDKN2Ahighmeningiomas and meningiomas with CDKN2A copy number loss shared common up-regulated cell cycling pathways. CDK4 mRNA expression was increased in CDKN2Ahighmeningiomas and both p16 and CDK4 protein were more abundant in CDKN2Ahighmeningiomas. CDKN2Ahighmeningiomas were frequently hypermethylated at the gene body and UTR compared to CDKN2Alowmeningiomas and found be more commonly Rb-deficient.

Conclusions

An intermediate level of CDKN2A mRNA expression appears to be optimal as significantly low (CDKN2A deleted) or high expression (CDKN2Ahigh) are associated with poorer outcomes clinically. Though CDK4 is elevated in CDKN2Ahighmeningiomas, Rb-deficiency may be more common in this group, leading to lack of response to CDK inhibitors.
FACTORS IMPACTED ON WELLBEING IN ADOLESCENT WHO HAVE FAMILY MEMBER WITH MENTAL DISORDER: A LITERATURE REVIEW
Authors: Tristiana Rr Dian , Rumambo Pandin Glorino , Yusuf Ah , Moses
Published: December 2022

Having a family member with mental disorder will affect their healthy family member life. This study to examine the factors impacted on adolescent well-being who have family member with mental disorder. This study was a literature review in two databases SCOPUS and Science which conducted by four steps: (1) identification of literature; (2) screening questions; (3) eligibility using inclusion criteria; and (4) assessment of the quality of the studies. This study found 17 article which then reviewed and analyzed. The study result found seven theme that impacted on well-being included the caregiving responsibilities; the caregiving perception; the caregiving supports; Coping; Caregiving burden; Caregiving positive effects; Psychological impact; Adaptation enhancing. This study the results show the need to explore the seven themes in relation to the conditions of well-being on adolescent who have family member with mental disorder.