bluuebunny/crossref_metadata_2025_split huggingface dataset:
The native distribution of a common legume shrub is limited by the range of its nitrogen‐fixing mutualist
Authors: Alon Moshe , Waitz Yoni , Finkel Omri M. , Sheffer Efrat 
Published: February 2024

Summary
Plant–microbe mutualisms, such as the legume‐rhizobium symbiosis, are influenced by the geographical distributions of both partners. However, limitations on the native range of legumes, resulting from the absence of a compatible mutualist, have rarely been explored.
We used a combination of a large‐scale field survey and controlled experiments to determine the realized niche of Calicotome villosa, an abundant and widespread legume shrub.
Soil type was a major factor affecting the distribution and abundance of C. villosa. In addition, we found a large region within its range in which neither C. villosa nor Bradyrhizobium, the bacterial genus that associates with it, were present. Seedlings grown in soil from this region failed to nodulate and were deficient in nitrogen. Inoculation of this soil with Bradyrhizobium isolated from root nodules of C. villosa resulted in the formation of nodules and higher growth rate, leaf N and shoot biomass compared with un‐inoculated plants.
We present evidence for the exclusion of a legume from parts of its native range by the absence of a compatible mutualist. This result highlights the importance of the co‐distribution of both the host plant and its mutualist when attempting to understand present and future geographical distributions of legumes.
A systematic review and meta‐analysis on absolute eosinophil counts and the risk of asthma in preschool children with wheezing: An EAACI Task Force Report
Authors: Adamiec Aleksander , Cieślik Maja , Mączka Katarzyna , Tarnoruda Joanna , Jensen Signe , Chawes Bo , Bønnelykke Klaus , Konradsen Jon R. , Söderhäll Cilla , Makrinioti Heidi , Camargo Carlos A. , Hasegawa Kohei , Ambrożej Dominika , Jartti Tuomas , Ruszczyński Marek , Feleszko Wojciech ,   for the EAACI Task Force on Preschool Wheeze
Published: February 2024

AbstractPreschool children with wheezing disorders pose diagnostic and therapeutic challenges and consume substantial healthcare resources. Peripheral eosinophil blood count (EBC) has been proposed as a potential indicator for future asthma development. This review by the European Academy of Allergy and Clinical Immunology (EAACI) Preschool Wheeze Task Force aimed to provide systematic evidence for the association between increased EBC and the risk of future asthma, as well as to identify potential cutoff values. In February 2023, a search of PubMed, EMBASE, and Cochrane Library databases was conducted to identify studies comparing EBCs in preschool children with wheezing who continued to wheeze later in life and those who did not. Included observational studies focused on children aged <6 years with a wheezing disorder, assessment of their EBCs, and subsequent asthma status. No language or publication date restrictions were applied. Among the initial 3394 studies screened, 10 were included in the final analysis, involving 1225 patients. The data from these studies demonstrated that high EBC in preschool children with wheezing is associated with future asthma development, with odds ratios of 1.90 (95% CI: 0.45–7.98, p = .38), 2.87 (95% CI: 1.38–5.95, p < .05), and 3.38 (95% CI: 1.72–6.64, p < .05) for cutoff values in the <300, 300–449, and ≥450 cells/μL ranges, respectively. Defining a specific cutoff point for an elevated EBC lacks consistency, but children with EBC >300 cells/μL are at increased risk of asthma. However, further research is needed due to the limitations of the included studies. Future investigations are necessary to fully elucidate the discussed association.
The C4 photosynthesis bifunctional enzymes, PDRPs, of maize are co‐opted to cytoplasmic viral replication complexes to promote infection of a prevalent potyvirus sugarcane mosaic virus
Authors: Xie Jipeng , Fei Xiaohong , Yan Qin , Jiang Tong , Li Zhifang , Chen Hui , Wang Baichen , Chao Qing , He Yueqiu , Fan Zaifeng , Wang Lijin , Wang Meng , Shi Liang , Zhou Tao 
Published: February 2024

SummaryIn maize, two pyruvate orthophosphate dikinase (PPDK) regulatory proteins, ZmPDRP1 and ZmPDRP2, are respectively specific to the chloroplast of mesophyll cells (MCs) and bundle sheath cells (BSCs). Functionally, ZmPDRP1/2 catalyse both phosphorylation/inactivation and dephosphorylation/activation of ZmPPDK, which is implicated as a major rate‐limiting enzyme in C4 photosynthesis of maize. Our study here showed that maize plants lacking ZmPDRP1 or silencing of ZmPDRP1/2 confer resistance to a prevalent potyvirus sugarcane mosaic virus (SCMV). We verified that the C‐terminal domain (CTD) of ZmPDRP1 plays a key role in promoting viral infection while independent of enzyme activity. Intriguingly, ZmPDRP1 and ZmPDRP2 re‐localize to cytoplasmic viral replication complexes (VRCs) following SCMV infection. We identified that SCMV‐encoded cytoplasmic inclusions protein CI targets directly ZmPDRP1 or ZmPDRP2 or their CTDs, leading to their re‐localization to cytoplasmic VRCs. Moreover, we found that CI could be degraded by the 26S proteasome system, while ZmPDRP1 and ZmPDRP2 could up‐regulate the accumulation level of CI through their CTDs by a yet unknown mechanism. Most importantly, with genetic, cell biological and biochemical approaches, we provide evidence that BSCs‐specific ZmPDRP2 could accumulate in MCs of Zmpdrp1 knockout (KO) lines, revealing a unique regulatory mechanism crossing different cell types to maintain balanced ZmPPDK phosphorylation, thereby to keep maize normal growth. Together, our findings uncover the genetic link of the two cell‐specific maize PDRPs, both of which are co‐opted to VRCs to promote viral protein accumulation for robust virus infection.
Protective effect of isoquercitrin on UVB‐induced injury in HaCaT cells and mice skin through anti‐inflammatory, antioxidant, and regulation of MAPK and JAK2‐STAT3 pathways
Authors: Li Yingyan , Ma Yunge , Yao Yike , Ru Guohua , Lan Chong , Li Liyan , Huang Tao 
Published: February 2024

AbstractNatural products are favored in the study of skin photodamage protection recently. Isoquercetin, namely 3‐O‐glucoside of quercetin, can be isolated from various plant species. In present research, the protective effect of isoquercitrin on UVB‐induced injury in cells and mice skin were investigated. Our study reveals that 400 μM of isoquercitrin exhibits the best viability on UVB‐irradiated HaCaT cells, and beneficial effects against oxidative stress UVB‐induced in skin tissue by decreasing the levels of reactive oxygen species (ROS) and malondialdehyde (MDA), and simultaneously enhancing the activity of superoxide dismutase (SOD). Additionally, isoquercitrin was identified as an anti‐inflammatory agent by reducing the level of COX‐2 by Western blot analysis, and inflammatory cytokines such as IL‐6, IL‐1β, and TNF‐α by ELISA, and UVB‐induced epidermal thickening evidenced by H&E staining. It also effectively prevented UVB‐induced collagen fibers from degradation identified by Masson staining. Isoquercitrin significantly inhibited MAPK pathway by downregulating the levels of AP‐1, MMP‐1, MMP‐3, phospho‐p38, phospho‐JNK, phospho‐ERK, cleaved caspase‐9, cleaved caspase‐3, and JAK2‐STAT3 pathway by western blot analysis. In conclusion, isoquercitrin pretreatment protected mice skin from UVB irradiation‐induced injury effectively, and the underlying mechanism may involve MAPK and JAK2‐STAT3 signaling pathways.
Inhibition and potentiation of the exercise pressor reflex by pharmacological modulation of TRPC6 in male rats
Authors: Ducrocq Guillaume P. , Anselmi Laura , Stella Salvatore L. , Copp Steven W. , Ruiz‐Velasco Victor , Kaufman Marc P. 
Published: February 2024

AbstractWe determined the role played by the transient receptor potential canonical 6 (TRPC6) channel in evoking the mechanical component of the exercise pressor reflex in male decerebrated Sprague–Dawley rats. TRPC6 channels were identified by quadruple‐labelled (DiI, TRPC6, neurofilament‐200 and peripherin) immunohistochemistry in dorsal root ganglion (DRG) cells innervating the triceps surae muscles (n = 12). The exercise pressor reflex was evoked by statically contracting the triceps surae muscles before and after injection of the TRPC6 antagonist BI‐749327 (n = 11; 12 μg kg−1) or SAR7334 (n = 11; 7 μg kg−1) or the TRPC6 positive modulator C20 (n = 11; 18 μg kg−1). Similar experiments were conducted while the muscles were passively stretched (n = 8–12), a manoeuvre that isolated the mechanical component of the reflex. Blood pressure, tension, renal sympathetic nerve activity (RSNA) and blood flow were recorded. Of the DRG cells innervating the triceps surae muscles, 85% stained positive for the TRPC6 antigen, and 45% of those cells co‐expressed neurofilament‐200. Both TRPC6 antagonists decreased the reflex pressor responses to static contraction (−32 to −42%; P < 0.05) and to passive stretch (−35 to −52%; P < 0.05), whereas C20 increased these responses (55–65%; P < 0.05). In addition, BI‐749327 decreased the peak and integrated RSNA responses to both static contraction (−39 to −43%; P < 0.05) and passive stretch (−56 to −62%; P < 0.05), whereas C20 increased the RSNA to passive stretch only. The onset latency of the decrease or increase in RSNA occurred within 2 s of the onset of the manoeuvres (P < 0.05). Collectively, our results show that TRPC6 plays a key role in evoking the mechanical component of the exercise pressor reflex.
imageKey points
The exercise pressor reflex plays a key role in the sympathetic and haemodynamic responses to exercise. This reflex is composed of two components, namely the mechanoreflex and the metaboreflex.
The receptors responsible for evoking the mechanoreflex are poorly documented. A good candidate for this function is the transient receptor potential canonical 6 (TRPC6) channel, which is activated by mechanical stimuli and expressed in dorsal root ganglia of rats.
Using two TRPC6 antagonists and one positive modulator, we investigated the role played by TRPC6 in evoking the mechanoreflex in decerebrated rats.
Blocking TRPC6 decreased the renal sympathetic and the pressor responses to both contraction and stretch, the latter being a manoeuvre that isolates the mechanoreflex. In contrast, the positive modulator increased the pressor reflex to contraction and stretch, in addition to the sympathetic response to stretch.
Our results provide strong support for a role played by the TRPC6 channel in evoking the mechanoreflex.
National study on the risks of COVID-19 infection for paediatric kidney transplant recipients: a retrospective, cross-sectional study
Authors: Withers Charlotte , Patel Rishil , Reynolds Ben C , Christian Martin , Muorah Mordi , Tse Yincent , Edwards Liz , Yadav Pallavi , Haq Shuman , Hegde Shivaram , Callaghan Chris J , Bamford Alasdair , Marks Stephen D 
Published: February 2024

IntroductionDuring the COVID-19 pandemic, evidence emerged that immunosuppressed children were less affected by COVID-19 infections compared with immunosuppressed adults. The aim of our study was to investigate how COVID-19 infections affected paediatric kidney transplant recipients (pKTR) in the UK.MethodsQuestionnaires regarding COVID-19 infection data and care of pKTR during the COVID-19 pandemic were sent to all 13 UK paediatric nephrology centres examining asymptomatic and symptomatic pKTR with positive COVID-19 PCR testing from 1 April 2020 to 1 December 2021.Results63 pKTR who were 3.1 (range 0.1–15) years post-transplantation had COVID-19 infection with positive SARS-CoV-2 PCR RNA. Classical COVID-19 symptoms were present in half of the patients; with atypical presentations including diarrhoea (13%) and lethargy (13%) also noted, while a third of patients were asymptomatic. Eighteen patients (28%) were hospitalised including five asymptomatic patients admitted for other reasons. No patients needed ventilation or intensive care admission, and one patient received supplemental oxygen. There was evidence of acute kidney injury (AKI) in 71% of patients, but no patients needed kidney replacement therapy with haemofiltration or dialysis.ConclusionWe report 10.4% of the UK paediatric renal transplantation population had documented COVID-19 infections with positive SARS-CoV-2 PCR RNA with 28% of those affected requiring hospitalisation. The increased incidence of AKI, particularly after the first wave of the COVID-19 pandemic, was possibly due to increased testing. There was low morbidity and mortality compared with the adult population.
Published research on the human health implications of climate change between 2012 and 2021: cross sectional study
Authors: Bartlett Victoria L , Doernberg Harry , Mooghali Maryam , Gupta Ravi , Wallach Joshua D , Nyhan Kate , Chen Kai , Ross Joseph S 
Published: February 2024

ObjectiveTo better understand the state of research on the effects of climate change on human health, including exposures, health conditions, populations, areas of the world studied, funding sources, and publication characteristics, with a focus on topics that are relevant for populations at risk.DesignCross sectional study.Data sourcesThe National Institute of Environmental Health Sciences climate change and human health literature portal, a curated bibliographical database of global peer reviewed research and grey literature was searched. The database combines searches of multiple search engines including PubMed, Web of Science, and Google Scholar, and includes added-value expert tagging of climate change exposures and health impacts.Eligibility criteriaInclusion criteria were peer reviewed, original research articles that investigated the health effects of climate change and were published in English from 2012 to 2021. After identification, a 10% random sample was selected to manually perform a detailed characterisation of research topics and publication information.Results10 325 original research articles were published between 2012 and 2021, and the number of articles increased by 23% annually. In a random sample of 1014 articles, several gaps were found in research topics that are particularly relevant to populations at risk, such as those in the global south (134 countries established through the United Nations Office for South-South Cooperation) (n=444; 43.8%), adults aged 65 years or older (n=195; 19.2%), and on topics related to human conflict and migration (n=25; 2.5%) and food and water quality and security (n=148; 14.6%). Additionally, fewer first authors were from the global south (n=349; 34.4%), which may partly explain why research focusing on these countries is disproportionally less.ConclusionsAlthough the body of research on the health effects of climate change has grown substantially over the past decade, including those with a focus on the global south, a disproportionate focus continues to be on countries in the global north and less at risk populations. Governments are the largest source of funding for such research, and governments, particularly in the global north, need to re-orient their climate and health research funding to support researchers in the global south and to be more inclusive of issues that are relevant to the global south.
Efficacy and safety of adjunctive oral therapy in Parkinson’s disease with motor complications: a systematic review and network meta-analysis
Authors: Sisodia Vibuthi , Dubbeld Lars , De Bie Rob M A , Duarte Gonçalo S , Costa João , Dijk Joke M 
Published: February 2024

BackgroundThe aim of this manuscript is to review the evidence and compare the efficacy and safety of catechol-O-methyltransferase inhibitors (COMT-Is), dopamine receptor agonists (DRAs) and monoamine-oxidase B inhibitors (MAOB-Is) as adjunctive treatment to levodopa in patients with Parkinson’s disease (PD) experiencing motor complications.MethodsIn this systematic review and network meta-analysis, literature searches were performed in MEDLINE and Embase to identify eligible randomised controlled trials (RCTs) with a minimal follow-up of at least 4 weeks published in English between 1980 and 2021. RCTs were included if either a COMT-I, DRA or MAOB-I was evaluated as an adjunctive therapy to levodopa in patients with PD experiencing motor complications and dyskinesia. The main outcomes included daily off-medication time, motor and non-motor examination scales, and adverse events including dyskinesia.Results74 RCTs reporting on 18 693 patients were included. All three studied drug classes decreased daily off-medication time compared with placebo (COMT-Is mean −0.8 hours (95% CI −1.0 to −0.6), DRAs −1.1 hours (95% CI −1.4 to −0.8), MAOB-Is −0.9 hours (95% CI −1.2 to −0.6)). Safety analysis showed an increased risk of dyskinesia for all three drug classes (COMT-Is OR 3.3 (95% CI 2.7 to 4.0), DRAs 3.0 (95% CI 2.5 to 3.5), MAOB-Is 1.6 (95% CI 1.2 to 2.2)). According to surface under the cumulative ranking curve scores, pramipexole IR was associated with the most favourable benefit–risk profile.ConclusionsCOMT-Is, DRAs and MAOB-Is effectively reduce motor complications and increase incidence of dyskinesia. In the network meta-analysis, adjunctive use of DRAs appeared most effective.
Accuracy of screening tests for cervical precancer in women living with HIV in low-resource settings: a paired prospective study in Lusaka, Zambia
Authors: Taghavi Katayoun , Moono Misinzo , Mwanahamuntu Mulindi , Roumet Marie , Limacher Andreas , Kapesa Herbert , Madliwa Thamsanqa , Rutjes Anne , Basu Partha , Low Nicola , Manasyan Albert , Bohlius Julia 
Published: February 2024

ObjectiveThis study aimed to provide evidence to improve cervical screening for women living with HIV (WLHIV). We assessed the accuracy of screening tests that can be used in low-resource settings and give results at the same visit.Methods and analysisWe conducted a paired, prospective study among consecutive eligible WLHIV, aged 18–65 years, receiving cervical cancer screening at one hospital in Lusaka, Zambia. The histopathological reference standard was multiple biopsies taken at two time points. The target condition was cervical intraepithelial neoplasia grade 2 and above (CIN2+). The index tests were high-risk human papillomavirus detection (hrHPV, Xpert HPV, Cepheid), portable colposcopy (Gynocular, Gynius) and visual inspection with acetic acid (VIA). Accuracy of stand-alone and test combinations were calculated as the point estimate with 95% CIs. A sensitivity analysis considered disease when only visible lesions were biopsied.ResultsWomen included in the study had well-controlled HIV infection (median CD4 count=542 cells/mm3) and all except one were on antiretroviral therapy. Among 371 participants with histopathological results, 27% (101/371) women had CIN2+ and 23% (23/101) were not detected by any index test. Sensitivity and specificity for stand-alone tests were: hrHPV, 67.3% (95% CI 57.7% to 75.7%) and 65.3% (95% CI 59.4% to 70.7%); Gynocular 51.5% (95% CI 41.9% to 61.0%) and 80.0% (95% CI 74.8% to 84.3%); and VIA 22.8% (95% CI 15.7% to 31.9%) and 92.6% (95% CI 88.8% to 95.2%), respectively. Combining tests did not improve test accuracy measures. All test accuracies improved in sensitivity analysis.ConclusionThe low accuracy of screening tests assessed might be explained by our reference standard, which reduced verification and misclassification biases. Better screening strategies for WLHIV in low-resource settings are urgently needed.Trial registration numberNCT03931083.
A systematic review and critical appraisal of menopause guidelines
Authors: Hemachandra Chandima , Taylor Sasha , Islam Rakibul M , Fooladi Ensieh , Davis Susan R 
Published: February 2024

Objective and rationaleTo identify and appraise current national and international clinical menopause guidance documents, and to extract and compare the recommendations of the most robust examples.DesignSystematic review.Data sourcesOvid MEDLINE, EMBASE, PsycINFO and Web of ScienceEligibility criteria for selecting studiesPractice guidance documents for menopause published from 2015 until 20 July 2023. Quality was assessed by the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument.ResultsTwenty-six guidance papers were identified. Of these, five clinical practice guidelines (CPGs) and one non-hormonal therapy position statement met AGREE II criteria of being at least of moderate quality. The five CPGs listed symptoms associated with the perimenopause and menopause to be vasomotor symptoms (VMS), disturbed sleep, musculoskeletal pain, decreased sexual function or desire, and mood disturbance (low mood, mood changes or depressive symptoms). Acknowledged potential long-term menopause consequences were urogenital atrophy, and increased risks of cardiovascular disease and osteoporosis. VMS and menopause-associated mood disturbance were the only consistent indications for systemic menopausal hormone therapy (MHT). Some CPGs supported MHT to prevent or treat osteoporosis, but specific guidance was lacking. None recommended MHT for cognitive symptoms or prevention of other chronic disease. Perimenopause-specific recommendations were scant. A neurokinin 3B antagonist, selective serotonin/norepinephrine (noradrenaline) reuptake inhibitors and gabapentin were recommended non-hormonal medications for VMS, and cognitive behavioural therapy and hypnosis were consistently considered as being of potential benefit.DiscussionThe highest quality CPGs consistently recommended MHT for VMS and menopause-associated mood disturbance, whereas clinical depression or cognitive symptoms, and cardiometabolic disease and dementia prevention were not treatment indications. Further research is needed to inform clinical recommendations for symptomatic perimenopausal women.
Bi-allelic variants in chromatoid body protein TDRD6 cause spermiogenesis defects and severe oligoasthenoteratozoospermia in humans
Authors: Guo Rui , Wu Huan , Zhu Xiaoyu , Wang Guanxiong , Hu Kaiqin , Li Kuokuo , Geng Hao , Xu Chuan , Zu Chenwan , Gao Yang , Tang Dongdong , Cao Yunxia , He Xiaojin 
Published: February 2024

BackgroundThe association between theTDRD6variants and human infertility remains unclear, as only one homozygous missense variant ofTDRD6was found to be associated with oligoasthenoteratozoospermia (OAT).MethodsWhole-exome sequencing and Sanger sequencing were employed to identify potential pathogenic variants ofTDRD6in infertile men. Histology, immunofluorescence, immunoblotting and ultrastructural analyses were conducted to clarify the structural and functional abnormalities of sperm in mutated patients.Tdrd6-knockout mice were generated using the CRISPR–Cas9 system. Total RNA-seq and single-cell RNA-seq (scRNA-seq) analyses were used to elucidate the underlying molecular mechanisms, followed by validation through quantitative RT-PCR and immunostaining. Intracytoplasmic sperm injection (ICSI) was also used to assess the efficacy of clinical treatment.ResultsBi-allelicTDRD6variants were identified in five unrelated Chinese individuals with OAT, including homozygous loss-of-function variants in two consanguineous families. Notably, besides reduced concentrations and impaired motility, a significant occurrence of acrosomal hypoplasia was detected in multiple spermatozoa among five patients. Using theTdrd6-deficient mice, we further elucidate the pivotal role of TDRD6 in spermiogenesis and acrosome identified. In addition, the mislocalisation of crucial chromatoid body components DDX4 (MVH) and UPF1 was also observed in round spermatids from patients harbouringTDRD6variants. ScRNA-seq analysis of germ cells from a patient withTDRD6variants revealed that TDRD6 regulates mRNA metabolism processes involved in spermatid differentiation and cytoplasmic translation.ConclusionOur findings strongly suggest that TDRD6 plays a conserved role in spermiogenesis and confirms the causal relationship betweenTDRD6variants and human OAT. Additionally, this study highlights the unfavourable ICSI outcomes in individuals with bi-allelicTDRD6variants, providing insights for potential clinical treatment strategies.