bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oral Huzhang granules for the treatment of acute gouty arthritis: protocol for a double-blind, randomized, controlled trial
Authors: Zhou Mi , Hua Liang , Wang Yi-Fei , Chen Si-Ting , Yang Chun-mei , Zhang Ming , Li Xin , Li Bin 
Published: April 2022

AbstractBackgroundAcute gouty arthritis (GA) is the main clinical manifestation and the most common initial symptom of gout. The treatment of acute GA involves the use of colchicine, non-steroidal anti-inflammatory drugs, and corticosteroids. Because of the side effects of these drugs, their clinical applications are limited. The use of traditional Chinese medicine for the treatment of acute GA has unique advantages. The aim of this trial is to clarify the treatment efficacy, safety, and recurrence control efficacy ofHuzhanggranules (HZG) in patients with GA showing dampness-heat syndrome.Methods/designThis double-blind, randomized, controlled trial was planned to be conducted between July 1, 2020, and December 31, 2022. A sample size of 267 participants (89 per group) with GA will be randomly assigned to three treatment groups in the ratio of 1:1:1: HZG, etoricoxib, and placebo groups. The study duration is 13 days, including a 1-day screening period, 5-day intervention period, and 1-week follow-up period. The primary outcome is analgesic effectiveness, assessed as pain in the worst-affected joint, which will be measured using the visual analog scale. Secondary outcomes include the patient’s assessment of pain in the primary study joint, patient’s global assessment of response to therapy, investigator’s global assessment of response to therapy, investigator’s assessment of tenderness and swelling of the study joint, and TCM syndromes. Furthermore, the number, nature, and severity of adverse events will be recorded.DiscussionThis study will provide evidence regarding the clinical efficacy and safety of Chinese medicine treatment for acute gouty arthritis. This study will provide noteworthy findings.Trial registrationClinicalTrials.govNCT04462666. Registered on July 05, 2020 (first version).
Worms and bugs of the gut: the search for diagnostic signatures using barcoding, and metagenomics–metabolomics
Authors: Papaiakovou Marina , Littlewood D. Timothy J. , Doyle Stephen R. , Gasser Robin B. , Cantacessi Cinzia 
Published: April 2022

AbstractGastrointestinal (GI) helminth infections cause significant morbidity in both humans and animals worldwide. Specific and sensitive diagnosis is central to the surveillance of such infections and to determine the effectiveness of treatment strategies used to control them. In this article, we: (i) assess the strengths and limitations of existing methods applied to the diagnosis of GI helminth infections of humans and livestock; (ii) examine high-throughput sequencing approaches, such as targeted molecular barcoding and shotgun sequencing, as tools to define the taxonomic composition of helminth infections; and (iii) discuss the current understanding of the interactions between helminths and microbiota in the host gut. Stool-based diagnostics are likely to serve as an important tool well into the future; improved diagnostics of helminths and their environment in the gut may assist the identification of biomarkers with the potential to define the health/disease status of individuals and populations, and to identify existing or emerging anthelmintic resistance.
Graphical Abstract
Alemtuzumab for refractory primary systemic vasculitis—a randomised controlled dose ranging clinical trial of efficacy and safety (ALEVIATE)
Authors: Gopaluni Seerapani , Smith Rona , Goymer Donna , Cahill Hugh , Broadhurst Elizabeth , Wallin Elizabeth , McClure Mark , Chaudhry Afzal , Jayne David 
Published: April 2022

Abstract
Background
Primary systemic vasculitis (PSV) is a heterogeneous group of autoimmune conditions. There is an unmet need for alternative therapies that lead to sustained remission in patients with refractory disease. Alemtuzumab, an anti-CD52 antibody, depletes lymphocytes for prolonged periods and, in retrospective studies, has induced sustained, treatment-free remissions in patients with refractory/relapsing vasculitis but has raised safety concerns of infection and secondary autoimmunity. This phase IIb clinical trial aimed to assess the efficacy and safety of alemtuzumab, at two different doses, in inducing remission in refractory vasculitis patients.

Methods
The ALEVIATE trial was a randomised, prospective, open-label, dose ranging clinical trial. Patients with refractory ANCA-associated vasculitis (AAV) or Behçet’s disease (BD) were randomised to receive either 60 mg or 30 mg alemtuzumab. Treatments were administered at baseline and 6 months or earlier where clinically appropriate. A maximum of three treatments were allowed within the 12-month study period.

Results
Twenty-three patients received at least one dose of alemtuzumab. Twelve had AAV, and 11 a diagnosis of BD. The median age was 40 years (range 28–44), with a prior disease duration of 61 months (42–103). Sixteen (70%) achieved either complete (6/23, 26%) or partial (10/23, 44%) response at 6 months. Eight (35%) maintained remission to the end of the trial without relapse. Ten severe adverse events were observed in 7 (30%) patients; 4 were related to alemtuzumab. There were no differences in clinical endpoints between the 60 and 30 mg alemtuzumab treatment groups.

Conclusion
In a selected group of refractory vasculitis patients, alemtuzumab led to remission in two thirds of patients at 6 months. Remission was maintained to 12 months in a third of the patients, and the safety profile was acceptable.

Trial registration
ClinicalTrials.gov identifier: NCT01405807, EudraCT Number: 2009-017087-17. Registered on April 07, 2011.
A multiepitope vaccine encoding four Eimeria epitopes with PLGA nanospheres: a novel vaccine candidate against coccidiosis in laying chickens
Authors: Yu ZhengQing , Chen SiYing , Huang JianMei , Ding WenXi , Chen YuFeng , Su JunZhi , Yan RuoFeng , Xu LiXin , Song XiaoKai , Li XiangRui 
Published: April 2022

AbstractWith a worldwide distribution, Eimeria spp. could result in serious economic losses to the poultry industry. Due to drug resistance and residues, there are no ideal drugs and vaccines against Eimeria spp. in food animals. In the current study, a bioinformatics approach was employed to design a multiepitope antigen, named NSLC protein, encoding antigenic epitopes of E. necatrix NA4, E. tenella SAG1, E. acervulina LDH, and E. maxima CDPK. Thereafter, the protective immunity of NSLC protein along with five adjuvants and two nanospheres in laying chickens was evaluated. Based on the humoral immunity, cellular immunity, oocyst burden, and the coefficient of growth, the optimum adjuvant was evaluated. Furthermore, the optimum immune route and dosage were also investigated according to the oocyst burden and coefficient of growth. Accompanied by promoted secretion of antibodies and enhanced CD4+ and CD8+ T lymphocyte proportions, NSLC proteins entrapped in PLGA nanospheres were more effective in stimulating protective immunity than other adjuvants or nanospheres, indicating that PLGA nanospheres were the optimum adjuvant for NSLC protein. In addition, a significantly inhibited oocyst burden and growth coefficient promotion were also observed in animals vaccinated with NSLC proteins entrapped in PLGA nanospheres, indicating that the optimum adjuvant for NSLC proteins was PLGA nanospheres. The results also suggested that the intramucosal route with PLGA nanospheres containing 300 μg of NSLC protein was the most efficient approach to induce protective immunity against the four Eimeria species. Collectively, PLGA nanospheres loaded with NSLC antigens are potential vaccine candidates against avian coccidiosis.
A two-stage detection method of copy-move forgery based on parallel feature fusion
Authors: Ye Wujian , Zeng Qingyuan , Peng Yihang , Liu Yijun , Chang Chin-Chen 
Published: April 2022

AbstractThe copy-move forgery refers to the copying and pasting of a region of the original image into the target region of the same image, which represents a typical tampering method with the characteristics of easy tampering and high-quality tampering. The existing single feature-based methods of forgery detection have certain shortcomings, such as high false alarm rate, low robustness, and low detection accuracy. To address these shortcomings, this paper proposes an improved two-stage detection method based on parallel feature fusion and an adaptive threshold generation algorithm. Firstly, the SLIC super-pixels segmentation algorithm is used for image preprocessing, and a similar region extraction algorithm without threshold is employed to obtain the suspected tampering regions with high similarity. Secondly, the parallel fusion feature is obtained based on the SIFT and HU features to express the characteristics of local regions. Then, the corresponding threshold value is generated based on the histogram of oriented gradient (HOG) to describe the texture characteristics of the obtained regions, which acts as a criterion to judge whether a region has been forged or not. The experimental results show that the proposed method outperforms the existing methods, achieving the accuracy of 99.01% and 98.5% on the MICC-F220 and MICC-F2000 datasets respectively. In addition, the proposed method has stronger robustness performance on COMOFOD dataset than the comparison methods.
Phase II Study of Selumetinib in Children and Young Adults With Tumors Harboring Activating Mitogen-Activated Protein Kinase Pathway Genetic Alterations: Arm E of the NCI-COG Pediatric MATCH Trial
Authors: Eckstein Olive S. , Allen Carl E. , Williams P. Mickey , Roy-Chowdhuri Sinchita , Patton David R. , Coffey Brent , Reid Joel M. , Piao Jin , Saguilig Lauren , Alonzo Todd A. , Berg Stacey L. , Ramirez Nilsa C. , Jaju Alok , Mhlanga Joyce , Fox Elizabeth , Hawkins Douglas S. , Mooney Margaret M. , Takebe Naoko , Tricoli James V. , Janeway Katherine A. , Seibel Nita L. , Parsons D. Williams 
Published: April 2022

PURPOSE The NCI-COG Pediatric MATCH trial assigns patients age 1-21 years with relapsed or refractory solid tumors, lymphomas, and histiocytic disorders to phase II studies of molecularly targeted therapies on the basis of detection of predefined genetic alterations. Patients with tumors harboring mutations or fusions driving activation of the mitogen-activated protein kinase (MAPK) pathway were treated with the MEK inhibitor selumetinib. METHODS Patients received selumetinib twice daily for 28-day cycles until disease progression or intolerable toxicity. The primary end point was objective response rate; secondary end points included progression-free survival and tolerability of selumetinib. RESULTS Twenty patients (median age: 14 years) were treated. All were evaluable for response and toxicities. The most frequent diagnoses were high-grade glioma (HGG; n = 7) and rhabdomyosarcoma (n = 7). Twenty-one actionable mutations were detected: hotspot mutations in KRAS (n = 8), NRAS (n = 3), and HRAS (n = 1), inactivating mutations in NF1 (n = 7), and BRAF V600E (n = 2). No objective responses were observed. Three patients had a best response of stable disease including two patients with HGG ( NF1 mutation, six cycles; KRAS mutation, 12 cycles). Six-month progression-free survival was 15% (95% CI, 4 to 34). Five patients (25%) experienced a grade 3 or higher adverse event that was possibly or probably attributable to study drug. CONCLUSION A national histology-agnostic molecular screening strategy was effective at identifying children and young adults eligible for treatment with selumetinib in the first Pediatric MATCH treatment arm to be completed. MEK inhibitors have demonstrated promising responses in some pediatric tumors (eg, low-grade glioma and plexiform neurofibroma). However, selumetinib in this cohort with treatment-refractory tumors harboring MAPK alterations demonstrated limited efficacy, indicating that pathway mutation status alone is insufficient to predict response to selumetinib monotherapy for pediatric cancers.
Long-read Amplicon Sequencing of the CYP21A2 in 48 Thai Patients With Steroid 21-Hydroxylase Deficiency
Authors: Tantirukdham Nithiphut , Sahakitrungruang Taninee , Chaisiwamongkol Ratikorn , Pongpanich Monnat , Srichomthong Chalurmpon , Assawapitaksakul Adjima , Buasong Aayalida , Tongkobpetch Siraprapa , Yeetong Patra , Shotelersuk Vorasuk 
Published: April 2022

Abstract

Context
Congenital adrenal hyperplasia is most commonly caused by 21-hydroxylase deficiency (21-OHD), an autosomal recessive disorder resulting from biallelic pathogenic variants (PVs) in CYP21A2. With a highly homologous pseudogene and various types of single nucleotide and complex structural variants, identification of PVs in CYP21A2 has been challenging.

Objective
To leverage long-read next-generation sequencing combined with locus-specific polymerase chain reaction (PCR) to detect PVs in CYP21A2 and to determine its diagnostic yield in patients with 21-OHD.

Methods
Forty-eight Thai patients with 21-OHD comprising 38 sporadic cases and 5 pairs of siblings were enrolled. Two previously described locus-specific PCR methods were performed. Amplicons were subject to long-read sequencing.

Results
Ninety-six PVs in CYP21A2 in the 48 patients were successfully identified. The combined techniques were able to detect 26 structural chimeric variants (27%; 26/96) in 22 patients with 18 having monoallelic and 4 having biallelic chimeras. The remaining PVs were pseudogene-derived mutations (63%; 60/96), entire gene deletions (2%; 2/96), missense variants (3%; 3/96), a splice-site variant (2%; 2/96), frameshift variants (2%; 2/96), and a nonsense variant (1%; 1/96). Notably, a splice-site variant, IVS7 + 1G &gt; T, which was identified in a pair of siblings, has not previously been reported.

Conclusions
Our approach exploiting locus-specific PCR and long-read DNA sequencing has a 100% diagnostic yield for our cohort of 48 patients with 21-OHD.
TOR signalling is required for host lipid metabolic remodelling and survival following enteric infection in Drosophila
Authors: Deshpande Rujuta , Lee Byoungchun , Qiao Yuemeng , Grewal Savraj S. 
Published: April 2022

ABSTRACT
When infected by enteric pathogenic bacteria, animals need to initiate local and whole-body defence strategies. Although most attention has focused on the role of innate immune anti-bacterial responses, less is known about how changes in host metabolism contribute to host defence. Using Drosophila as a model system, we identify induction of intestinal target-of-rapamycin (TOR) kinase signalling as a key adaptive metabolic response to enteric infection. We find that enteric infection induces both local and systemic induction of TOR independently of the Immune deficiency (IMD) innate immune pathway, and we see that TOR functions together with IMD signalling to promote infection survival. These protective effects of TOR signalling are associated with remodelling of host lipid metabolism. Thus, we see that TOR is required to limit excessive infection-mediated wasting of host lipid stores by promoting an increase in the levels of gut- and fat body-expressed lipid synthesis genes. Our data support a model in which induction of TOR represents a host tolerance response to counteract infection-mediated lipid wasting in order to promote survival.
This article has an associated First Person interview with the first author of the paper.
Annexin A2 and Ahnak control cortical NuMA–dynein localization and mitotic spindle orientation
Authors: Pascal Aude , Gallaud Emmanuel , Giet Regis , Benaud Christelle 
Published: April 2022

ABSTRACT
Proper mitotic spindle orientation depends on the correct anchorage of astral microtubules to the cortex. It relies on the remodeling of the cell cortex, a process not fully understood. Annexin A2 (Anx2; also known as ANXA2) is a protein known to be involved in cortical domain remodeling. Here, we report that in HeLa cell early mitosis, Anx2 recruits the scaffold protein Ahnak at the cell cortex facing spindle poles, and the distribution of both proteins is controlled by cell adhesion. Depletion of either protein or impaired cortical Ahnak localization result in delayed anaphase onset and unstable spindle anchoring, which leads to altered spindle orientation. We find that Ahnak is present in a complex with dynein–dynactin. Furthermore, Ahnak and Anx2 are required for correct dynein and NuMA (also known as NUMA1) cortical localization and dynamics. We propose that the Ahnak–Anx2 complex influences the cortical organization of the astral microtubule-anchoring complex, and thereby mitotic spindle positioning in human cells. This article has an associated First Person interview with the first author of the paper.
Emerin regulation of nuclear stiffness is required for fast amoeboid migration in confined environments
Authors: Lavenus Sandrine B. , Vosatka Karl W. , Caruso Alexa P. , Ullo Maria F. , Khan Ayesha , Logue Jeremy S. 
Published: April 2022

ABSTRACT
When metastasizing, tumor cells must traverse environments with diverse physicochemical properties. Recently, the cell nucleus has emerged as a major regulator of the transition from mesenchymal to fast amoeboid (leader bleb-based) migration. Here, we demonstrate that increasing nuclear stiffness through elevating lamin A, inhibits fast amoeboid migration in melanoma cells. Importantly, nuclei may respond to force through stiffening. A key factor in this process is the inner nuclear membrane (INM) protein emerin. Accordingly, we determined the role of emerin in regulating fast amoeboid migration. Strikingly, we found that both the up- and downregulation of emerin results in an inhibition of fast amoeboid migration. However, when key Src phosphorylation sites were removed, upregulation of emerin no longer inhibited fast amoeboid migration. Interestingly, as measured by using a Src biosensor, activity of Src was low in cells within a confined environment. Thus, the fast amoeboid migration of melanoma cells depends on the precise calibration of emerin activity.
A perspective on insect water balance
Authors: O’Donnell Michael J. 
Published: April 2022

ABSTRACT
Insects have a large ratio of surface area to volume because of their small size; thus, they face the potential for desiccation in the terrestrial environment. Nonetheless, they constitute over half of identified species and their success on land can be attributed, in part, to adaptations that limit water loss and allow for effective gains of water from food, fluids or atmospheric water vapour. Reduction of water loss from the gut involves sophisticated mechanisms of ion recycling and water recovery by epithelia of the Malpighian tubules and hindgut. Water loss across the body surface is greatly reduced by the evolution of very thin but highly impermeable lipid-rich layers in the epicuticle. Respiratory water loss can be reduced through effective spiracular control mechanisms and by mechanisms for convective rather than diffusive gas exchange. In addition to extracting water from food sources, some insects are capable of absorption of atmospheric water vapour through processes that have evolved independently in multiple groups.
Mental resilience and professional burnout among teachers
Authors: Pluskota Małgorzata , Zdziarski Krzysztof 
Published: April 2022

W artykule podjęto próbę przedstawienia zależności między prężnością psychologiczną, a wypaleniem zawodowym nauczycieli szkół podstawowych, ponadpodstawowych oraz uczelni wyższych. W pierwszej części zostały przybliżone zagadnienia prężności psychicznej oraz wypalenia zawodowego. Do przeprowadzenia badania wykorzystano Kwestionariusz Oceny Prężności (KOP-26) i Kwestionariusz LBQ, który ocenia poziom wypalenia zawodowego. Dalsza część artykułu przedstawia wyniki badań w obszarze zależności między prężnością psychiczną i jej składowymi (kompetencjami osobistymi, relacjami rodzinnymi oraz kompetencjami społecznymi) a syndromem wypalenia zawodowego. Nauczyciele wykazali istotne różnice pod względem poziomu prężności psychicznej i różnili się stopniem wypalenia zawodowego. Wykazano silną korelację pomiędzy prężnością psychiczną a wypaleniem zawodowym nauczycieli. Nie zauważono wyższego stopnia wypalenia zawodowego wśród nauczycieli niższych etapów nauczania. Nauczyciele uczelni wyższych charakteryzowali się minimalnie wyższym stopniem wypalenia zawodowego. Ponadto wykazano, że wsparcie rodziny ma znaczący związek w niwelowaniu wypalenia zawodowego. We wnioskach wskazano potrzebę wprowadzenia profilaktyki wypalenia zawodowego wśród nauczycieli poprzez psychoedukację w zakresie umiejętności składających się na poszczególne elementy prężności psychicznej oraz pogłębienie badań wśród konkretnej grupy nauczycieli.
Transfibular total ankle arthroplasty
Authors: Maccario Camilla , Paoli Tommaso , Romano Fausto , D’Ambrosi Riccardo , Indino Cristian , Usuelli Federico G. 
Published: April 2022

Aims This study reports updates the previously published two-year clinical, functional, and radiological results of a group of patients who underwent transfibular total ankle arthroplasty (TAA), with follow-up extended to a minimum of five years. Methods We prospectively evaluated 89 patients who underwent transfibular TAA for end-stage osteoarthritis. Patients’ clinical and radiological examinations were collected pre- and postoperatively at six months and then annually for up to five years of follow-up. Three patients were lost at the final follow-up with a total of 86 patients at the final follow-up. Results A total of 86 patients were evaluated at a mean follow-up of 65.4 months (60 to 90). At five-year follow-up, statistically significant improvements (p < 0.001) were found in the mean American Orthopaedic Foot & Ankle Society Ankle Hindfoot Score (from 33.8 (SD 14.3) to 86.1 (SD 8.8)), visual analogue scale for pain (from 8.5 (SD 1.7) to 1.5 (SD 1.2)), Short Form-12 Physical and Mental Component Scores (from 29.9 (SD 6.7) and 43.3 (SD 8.6) to 47.3 (SD 7.5) and 52.2 (SD 8.0), respectively), and mean ankle dorsiflexion and plantarflexion (from 6.2° (SD 5.5°) and 9.6° (SD 5.8°) to 23.9° (SD 7.7°) and 16.9° (SD 7.2°), respectively). Radiologically, the implants maintained neutral alignment without subsidence. Tibial or talar radiolucency was found in eight patients, but none of these patients was symptomatic. At five-year follow up, 97.7% of implants (95% confidence interval 91.2 to 99.4) were free from revision or removal with 84 implants at risk. We recorded two cases (2.3%) of failure for septic loosening. Conclusion Transfibular TAA is safe and effective with a high survival rate at mid-term follow-up and satisfactory clinical and radiological results. Further studies are required to determine the long-term performance of these implants. Cite this article: Bone Joint J 2022;104-B(4):472–478.