bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanisms underlying DMARD inefficacy in difficult-to-treat rheumatoid arthritis: a narrative review with systematic literature search
Authors: Roodenrijs Nadia M T , Welsing Paco M J , van Roon Joël , Schoneveld Jan L M , van der Goes Marlies C , Nagy György , Townsend Michael J , van Laar Jacob M 
Published: March 2022

AbstractManagement of RA patients has significantly improved over the past decades. However, a substantial proportion of patients is difficult-to-treat (D2T), remaining symptomatic after failing biological and/or targeted synthetic DMARDs. Multiple factors can contribute to D2T RA, including treatment non-adherence, comorbidities and co-existing mimicking diseases (e.g. fibromyalgia). Additionally, currently available biological and/or targeted synthetic DMARDs may be truly ineffective (‘true’ refractory RA) and/or lead to unacceptable side effects. In this narrative review based on a systematic literature search, an overview of underlying (immune) mechanisms is presented. Potential scenarios are discussed including the influence of different levels of gene expression and clinical characteristics. Although the exact underlying mechanisms remain largely unknown, the heterogeneity between individual patients supports the assumption that D2T RA is a syndrome involving different pathogenic mechanisms.
Neuropsychological Performance Among Individuals at Clinical High-Risk for Psychosis vs Putatively Low-Risk Peers With Other Psychopathology: A Systematic Review and Meta-Analysis
Authors: Millman Zachary B , Roemer Caroline , Vargas Teresa , Schiffman Jason , Mittal Vijay A , Gold James M 
Published: February 2022

Abstract

Background and Hypothesis
Youth at clinical high-risk (CHR) for psychosis present with neuropsychological impairments relative to healthy controls (HC), but whether these impairments are distinguishable from those seen among putatively lower risk peers with other psychopathology remains unknown. We hypothesized that any excess impairment among CHR cohorts beyond that seen in other clinical groups is minimal and accounted for by the proportion who transition to psychosis (CHR-T).

Study Design
We performed a systematic review and meta-analysis of studies comparing cognitive performance among CHR youth to clinical comparators (CC) who either sought mental health services but did not meet CHR criteria or presented with verified nonpsychotic psychopathology.

Study Results
Twenty-one studies were included representing nearly 4000 participants. Individuals at CHR showed substantial cognitive impairments relative to HC (eg, global cognition: g = −0.48 [−0.60, −0.34]), but minimal impairments relative to CC (eg, global cognition: g = −0.13 [−0.20, −0.06]). Any excess impairment among CHR was almost entirely attributable to CHR-T; impairment among youth at CHR without transition (CHR-NT) was typically indistinguishable from CC (eg, global cognition, CHR-T: g = −0.42 [−0.64, −0.19], CHR-NT: g = −0.09 [−0.18, 0.00]; processing speed, CHR-T: g = −0.59 [−0.82, −0.37], CHR-NT: g = −0.12 [−0.25, 0.07]; working memory, CHR-T: g = −0.42 [−0.62, −0.22], CHR-NT: g = −0.03 [−0.14, 0.08]).

Conclusions
Neurocognitive impairment in CHR cohorts should be interpreted cautiously when psychosis or even CHR status is the specific clinical syndrome of interest as these impairments most likely represent a transdiagnostic vs psychosis-specific vulnerability.
Production performance, nutrient use efficiency, and predicted enteric methane emissions in dairy cows under confinement or grazing management system
Authors: Brito Andre F , Almeida Kleves V , Oliveira Andre S 
Published: February 2022

Abstract
There has been an intense debate regarding the economic, social, and environmental sustainability of confinement versus grazing dairy systems. Our goal was to conduct a meta-analysis to compare dry matter intake, milk yield and composition, nutrient use efficiency (i.e., feed efficiency, milk N efficiency), and predicted enteric CH4 emissions using studies that simultaneously evaluated confinement and grazing. We were able to include in the meta-analysis 8 peer-reviewed articles that met the following selection criteria: (1) publication between 1991 and 2021 in English language, (2) report either SEM or SD, (3) inclusion of at least 1 confinement [total mixed ration or fresh cut herbage fed indoors (i.e., zero-grazing)] and 1 grazing treatment in the same study, and (4) use of markers (internal or external) to estimate herbage dry matter intake. Two unpublished experiments were added to the data set resulting in a total of 10 studies for comparing confinement and grazing. The magnitude of the effect (i.e., effect size) was evaluated using weighted raw mean differences between grazing and confinement systems for a random effect model. Enteric CH4 production was predicted as follows: CH4 (g/d) = 33.2 (13.54) + 13.6 (0.33) × dry matter intake + 2.43 (0.245) × neutral detergent fiber. Dry matter intake (–9.5%), milk yield (–9.3%), milk fat yield (–5.8%), milk protein yield (–10%), and energy-corrected milk (–12%) all decreased in grazing versus confined dairy cows. In contrast, concentration of milk fat and feed efficiency (energy-corrected milk/dry matter intake) were not affected by management system. Whereas milk protein concentration increased, milk nitrogen (N) efficiency (milk N/N intake) tended to decrease in grazing compared with confinement. Predicted enteric CH4 production was 6.1% lower in grazing than confined dairy cows. However, CH4 yield (g/kg of dry matter intake) and CH4 intensity (g/kg of energy-corrected milk) did not change between confinement and grazing. In conclusion, while production performance decreased in grazing dairy cows, nutrient use efficiency and predicted enteric CH4 emissions were relatively similar in both management systems. Results of our meta-analysis should be interpreted with caution due to the small number of studies that met our inclusion criteria leading to a limited number of treatment mean comparisons.
High Diversity of emm Types and Marked Tetracycline Resistance of Group A Streptococci and Other ß-Hemolytic Streptococci in Gabon, Central Africa
Authors: Arnold Benjamin , Bélard Sabine , Alabi Abraham , Hufnagel Markus , Berner Reinhard , Toepfner Nicole 
Published: February 2022

Background:
Group A ß-hemolytic streptococcus (GABHS) is a leading pathogen worldwide and post-streptococcal sequelae is a major cause of morbidity and mortality in resource-limited countries. The M protein (coded by the emm gene) is a key virulence factor and a component of GABHS vaccine candidates. As data on BHS in Central Africa are scarce, antibiotic resistance, emm diversity and potential vaccine coverage were investigated.

Methods:
In a prospective cross-sectional study, 1014 Gabonese were screened for streptococcal throat carriage, tonsillopharyngitis and pyoderma by throat and skin smear tests. All BHS were isolated, species were identified and analysis of antibiotic resistance, emm types and emm clusters was performed.

Results:
One hundred sixty-five BHS were detected, comprising 76 GABHS, 36 group C ß-hemolytic streptococcus (GCBHS) and 53 group G ß-hemolytic streptococcus (GGBHS) in 140 carrier, 9 tonsillopharyngitis and 16 pyoderma isolates. Eighty percentage of GABHS, 78% of GCBHS and 79% of GGBHS were tetracycline resistant. Forty-six emm types were identified. GABHS emm58, emm65 and emm81 were most prevalent (26%). Emm diversity of GABHS was the highest, GCBHS and GGBHS were less divers. Every second GABHS, every third GCBHS and every tenth GGBHS carrier was colonized with emm types detected in tonsillopharyngitis or pyoderma isolates.

Conclusions:
Tetracycline resistance and emm type diversity was high among BHS carriers in Gabon with a potential coverage of 58% by the 30-valent GABHS vaccine. A relevant overlap of carrier emm types with emm types found in tonsillopharyngitis and pyoderma characterizes a shared pool of circulating BHS strains.
Suicide Deaths Before and During the Coronavirus Disease 2019 Pandemic
Authors: Rossom Rebecca C. , Penfold Robert B. , Owen-Smith Ashli A. , Simon Greg E. , Ahmedani Brian K. 
Published: March 2022

Introduction:
With stressors that are often associated with suicide increasing during the coronavirus disease 2019 (COVID-19) pandemic, there has been concern that suicide mortality rates may also be increasing. Our objective was to determine whether suicide mortality rates increased during the COVID-19 pandemic.

Methods:
We conducted an interrupted time-series study using data from January 2019 through December 2020 from 2 large integrated health care systems. The population at risk included all patients or individuals enrolled in a health plan at HealthPartners in Minnesota or Henry Ford Health System in Michigan. The primary outcome was change in suicide mortality rates, expressed as annualized crude rates of suicide death per 100,000 people in 10 months following the start of the pandemic in March 2020 compared with the 14 months prior.

Results:
There were 6,434,675 people at risk in the sample, with 55% women and a diverse sample across ages, race/ethnicity, and insurance type. From January 2019 through February 2020, there was a slow increase in the suicide mortality rate, with rates then decreasing by 0.45 per 100,000 people per month from March 2020 through December 2020 (SE=0.19, P=0.03).

Conclusions:
Overall suicide mortality rates did not increase with the pandemic, and in fact slightly declined from March to December 2020. Our findings should be confirmed across other settings and, when available, using final adjudicated state mortality data.
Multivariate Genomic Architecture of Cortical Thickness and Surface Area at Multiple Levels of Analysis
Authors: Grotzinger Andrew D. , Mallard Travis T. , Liu Zhaowen , Seidlitz Jakob , Ge Tian , Smoller Jordan W. 
Published: February 2022

AbstractRecent work in imaging genetics suggests high levels of genetic overlap within cortical regions for cortical thickness (CT) and surface area (SA). We model this multivariate system of genetic relationships by applying Genomic Structural Equation Modeling (Genomic SEM) to parsimoniously define five genomic brain factors for both CT and SA. We reify these factors by demonstrating the generalizability of the model in a semi-independent sample and show that the factors align with biologically and functionally relevant parcellations of the cortex. We apply Stratified Genomic SEM to identify specific categories of genes (e.g., neuronal cell types) that are disproportionately associated with pleiotropy across specific subclusters of brain regions, as indexed by the genomic factors. Finally, we examine genetic associations with psychiatric and cognitive correlates, finding that SA is associated with both broad aspects of cognitive function and specific risk pathways for psychiatric disorders. These analyses provide key insights into the multivariate genomic architecture of two critical features of the cerebral cortex.
Astrocytic Ca2+ signals partake in inhibitory neurovascular coupling in a brain state-dependent manner
Authors: Krogsgaard Aske , Sperling Leonora , Dahlqvist Matilda , Thomsen Kirsten , Vydmantaite Gabriele , Lauritzen Martin , Lind Barbara Lykke 
Published: February 2022

AbstractNeurovascular coupling (NVC) modulates cerebral blood flow to match increased metabolic demand during neuronal excitation. Activation of inhibitory interneurons also increase blood flow, but the basis for this inhibitory NVC is unclear. We performed two-photon microscopy in awake mice to examine the correlation between astrocytic Ca2+ and NVC, evoked by activity in either all (VGATIN) or parvalbumin-positive GABAergic interneurons (PVIN). Optogenetic stimulation of VGATIN and PVIN in the somatosensory cortex triggered astrocytic Ca2+ increases that were abolished by anaesthesia. PVIN evoked astrocytic Ca2+ responses with a short latency that preceded NVC, whereas VGATIN evoked Ca2+ increases that were delayed relative to the NVC response. The early onset in PVIN evoked Ca2+ increases dependent on noradrenaline release from locus coeruleus, which also affected inhibitory NVC. Therefore, NVC mechanisms should be studied in awake mice and, though the relationship between interneuron activity and astrocytic Ca2+ is complex, we found a correlation between astrocyte activity and NVC in PVIN.
Direct and delayed synergistic effects of marine heatwaves, metals and food limitation on tropical reef-associated fish larvae
Authors: Le Minh-Hoang , Dinh Khuong V. , Vo Xuan Thi , Pham Hung Quoc 
Published: February 2022

AbstractTropical fish are fast-growing and high energetic-demand organisms, which can be highly vulnerable to long-lasting effects of heat stress and pollution, particularly under food shortages. We tested this by assessing highly complex direct and delayed interactive effects of an extreme temperature (32°C) from a simulated marine heatwave (MHW), copper (Cu, 0, 100, 150 and 175 µg L-1) and food availability (limited and saturated food) on larvae of a tropical, reef-associated seaperch (Psammoperca waigiensis). Cu, MHW, and food limitation independently reduced survival and growth, partly explained by reduced feeding. The negative effect of Cu on fish survival was more substantial under MHW, particularly under limited food. Delayed interactive effects of Cu, MHW, and food limitation were still lethal to fish larvae during the post-exposure period. These results indicate that reef-associated fish larvae are highly vulnerable to these dominant stressors, impairing their ecological function as predators in the coral reefs.Graphical abstract
Multisensory interactions on auditory and somatosensory information in expert pianists
Authors: Hirano Masato , Furuya Shinichi 
Published: February 2022

AbstractFine-tuned sensory functions are bases of efficient motor control and learning and typically characterize skilled individuals. Although numerous studies demonstrated enhanced unimodal sensory functions at both neural and behavioral levels in skilled individuals, little is known about their multisensory interaction, especially multisensory integration and selective attention that involve volitional control of information derived from multiple sensory organs. Here, we show unique multisensory interaction functions of expert pianists. Expert pianists and musically untrained individuals performed five sets of intensity discrimination tasks at the auditory and somatosensory modalities with different conditions: (1) auditory stimulus, (2) somatosensory stimulus, (3) congruent auditory and somatosensory stimuli (i.e., multisensory integration), (4) auditory and task-irrelevant somatosensory stimuli, and (5) somatosensory and task-irrelevant auditory stimuli. In the fourth and fifth conditions, participants were instructed to ignore a task-irrelevant stimulus and to pay attention to a task-relevant stimulus (i.e., selective attention). The unimodal intensity discrimination of the pianists was superior to that of the nonmusicians at the auditory modality but not at the somatosensory modality. While the discrimination perception was superior in the condition (3) compared to the better one of the individual unimodal conditions (i.e., conditions 1 and 2) only in the pianists, the task-irrelevant somatosensory stimulus worsened the auditory discrimination more in the pianists than the nonmusicians. These findings indicate efficient processing of multisensory information in expert pianists, which enables to benefit from multisensory integration of the auditory and somatosensory information, but exacerbates top-down selective inhibition of somatosensory information during auditory processing.
Development of duplex real time PCR for quick detection of Cryptosporidia in goats
Authors: Sharma Atul Kumar , Gururaj K. , Sharma Rama , Goel Anjana , Paul Souvik , Sharma Dinesh Kumar 
Published: February 2022

AbstractCryptosporidium spp. is the most important foodborne and waterborne pathogens and the leading cause of mortality from foodborne and waterborne gastrointestinal disease. In neonates of domestic animals it is associated with consistent diarrhoea and dehydration. Cryptosporidium infection begins with the ingestion of sporulated oocytes disseminated by carrier animals that consistently contaminate the environment. Many diagnostic tests are available including microscopy, antigen trap ELISA, but none of the diagnostic tests available currently cannot differentiate between active and passive infection in the host. In the current study, to address this challenge an mRNA based duplex TaqMan® probe PCR (dRT-qPCR) was developed to target the Cryptosporidium oocyst wall protein (COWP) gene and 18ssu rRNA gene in a single tube that can detect metabolically active Cryptosporidial oocysts. The mRNA transcripts are the direct indicator of any actively replicating cell and it will help decipher the active stages of its lifecycle in host. This diagnostic assay was standardized by computing transcript copy number-based limit of detection. For COWP and 188ssu rRNA genes the limit of detection was 7.08×1004 and 5.95×1005 respectively. During active infections the oocyst wall protein will be active and so its COWP gene transcripts will act as marker for active infection. While transcripts for 18SSU rRNA are constitutively expressing in Cryptosporidial life cycle. This current diagnostic assay will be a quantitative marker that will help assess active stages of Cryptosporidium infection in neonates. The disease dynamics will help better understand to formulate the control strategies and contain infection among the healthy animals.ImportanceCryptosporidiosis is an important neonatal disease affecting goats causing diarrhoea, dehydration and stunted growth. For diagnosing this condition, many diagnostic tests are available including microscopy, immunological tests, but none of the diagnostic tests available currently can differentiate between active and passive infection in the host. The mRNA transcripts are the direct indicator of any actively replicating cell and especially in intracellular parasites it will help decipher the infective stages of a lifecycle in the host, and hence the test was developed in a reverse transcriptional format in a duplex mode. The currently developed diagnostic assay for cryptosporidiosis was evaluated for sensitivity using Limit of detection (LOD). This diagnostic test will act as a quantitative marker to aid in detecting active stages of Cryptosporidium infection in neonatal goats and will eventually lead to better control strategies for managing cryptosporidial infections in the future.
Booster protection against Omicron infection in a highly vaccinated cohort
Authors: Tai Caroline G. , Maragakis Lisa L. , Connolly Sarah , DiFiori John , Sims Leroy , Adams Eleanor , Anderson Deverick J. , Merson Michael H. , Ho David D. , Grad Yonatan , Mack Christina DeFilippo 
Published: February 2022

ABSTRACTBackgroundEvaluation of COVID-19 vaccine booster effectiveness is essential as new variants of SARS-CoV-2 emerge. Data support the effectiveness of boosters in preventing severe disease and hospitalization; however, the real-world impact on reducing incident SARS-CoV-2 infections across specific variants is not yet clear.ObjectivesAssess the impact of COVID-19 boosters on protection against SARS-CoV-2 infection in a real-world setting from a highly vaccinated (99%) population curated from a linked database with test results, vaccination history, patient demographics, and genomic sequencing information from the National Basketball Association (NBA).MethodsIn this population, 1,613 fully vaccinated staff and players (median age 34.5 years, 88% male) who tested at least once between 1 December 2021 and 5 January 2022, were analyzed. Individuals were tested at the time of reporting any symptom, regardless of severity, after known exposure per self-report or contact tracing and/or during enhanced surveillance. Boosted individuals (n=1260) were compared to fully vaccinated and booster eligible individuals (n=162), defined as 2 months post-JNJ-78436735 or 5-months post-second dose of mRNA vaccine. Individuals not yet eligible for a booster and those who recovered from COVID-19 between 1 November and 30 November, 2021 (n=25) were examined in secondary analyses but excluded from the primary comparison. Individuals who were not fully vaccinated (n=27) or who received a booster within 14 days during or prior to the observation period (n=916) were excluded.ResultsIn this closely monitored population, fully vaccinated booster-eligible individuals were 2.6 times more likely (RR = 2.6, 95% CI: 2.2 to 3.0, p<0.0001) to have a confirmed COVID-19 infection than boosted individuals. Secondary analysis including non-boosted individuals with recent vaccination or recent SARS-CoV-2 infection found that non-boosted individuals were at greater risk of infection compared with boosted individuals (RR = 2.1, 95% CI: 1.8 to 2.4, p<0.001). Results were similar when stratified by primary vaccination type with overlapping confidence intervals. No hospitalizations or deaths were observed in this cohort. Genetic sequencing confirmed 93% of infections to be Omicron (among n=330 sequenced).ConclusionsThese results highlight the protective benefit of boosters against incident SARS-CoV-19 infection, not only for severe symptoms and death. Assessment of booster effectiveness remains vital for COVID-19 vaccines as new variants of SARS-CoV-2 emerge, as there is still uncertainty around performance in real-world settings. These data are needed to convince the general public that boosters remain effective at preventing in the spread of COVID-19.
Influence of Lamina Vastoadductoria Dissection on the Outcomes of Femoral Artery Extensive Lesion Stenting: A Pilot Randomised Investigation
Authors: Karpenko Andrey A. , Rabtsun Artem A. , Popova Irina V. , Saaya Shoraan B. , Gostev Alexandr A. , Ignatenko Pavel V. , Starodubtsev Vladimir B. , Cheban Alexey V. 
Published: February 2022

AbstractObjectiveAim of the study was to improve the immediate and long-term results of stenting of the superficial femoral artery in extended lesions with the changing of the biomechanics of SFA and of the first portion of the popliteal artery.MethodsPilot randomized prospective single-center study were included 70 patients. Patients were randomized into two groups in 1×1 format for 35 people using the envelope method. Self-expanding bare metal stents were used in all cases. At the first group standard revascularization procedures with SFA stenting were performed; in the second group, the superficial femoral artery stenting was supplemented with fasciotomy in the Hunter’s canal with the superficial femoral artery intersection. The total observation period was 2 years. During the observation period an assessment of the clinical symptoms of the lower extremities, measurement of the ankle-brachial index and ultrasound duplex scanning of the operated segment were performed.ResultsAll procedures in both groups were successfully performed. Primary patency through 24 months was 28.5% (10 of 35) in group 1 and 60% (21 of 35) in group 2 (p=0,015).ConclusionsChanging the biomechanical properties of the distal of the superficial femoral artery segment and of the first portion of the popliteal artery is safe and contributes to the primary patency improvement during the stenting of extended of the superficial femoral artery lesions compared to standard SFA stenting. Dissection of the lamina vastoadductoria with transection of the collateral branches of the knee joint network reduces frequent and severe damages of stents after the stenting of the superficial femoral artery extended lesion.According to the frequency of complications in the early and mid-term postoperative period, limb salvage, mortality and the secondary patency rates, the new method is comparable with standard of the superficial femoral artery stenting.