bluuebunny/crossref_metadata_2025 huggingface dataset:
Systemic inflammation score as a preoperative prognostic factor for patients with pT2–T4 resectable gastric cancer: a retrospective study
Authors: Matsumoto Takuro , Ohki Shinji , Kaneta Akinao , Matsuishi Akira , Maruyama Yuya , Yamada Leo , Tada Takeshi , Hanayama Hiroyuki , Watanabe Yohei , Hayase Suguru , Okayama Hirokazu , Sakamoto Wataru , Momma Tomoyuki , Saze Zenichiro , Kono Koji
Published: January 2023

Background

Systemic inflammation has been reported to be associated with cancer progression and metastasis. Systemic inflammation score (SIS), calculated from preoperative serum albumin level and lymphocyte-to-monocyte ratio, has been shown to be a novel prognostic factor for several types of tumors. This study aimed to evaluate the prognostic value of the SIS in patients with pT2–4 resectable gastric cancer (GC).

Methods

Total 97 patients with pT2–4 GC who underwent curative surgery from 322 cases between 2009 and 2015 in Fukushima Medical University Hospital were included. We performed univariate and multivariate analyses to evaluate the usefulness of preoperative SIS and other prognostic factors for relapse-free survival (RFS) and overall survival (OS).

Results

The higher SIS score was associated with undifferentiated cancer and recurrence. Univariate analysis of RFS identified deeper tumor invasion and higher SIS were significant risk factors and multivariate analysis revealed that both of them were independent prognostic factors for RFS. As for OS, age, tumor invasion, SIS and LNR were significantly correlated with RFS. In multivariate analysis, tumor invasion, SIS and LNR were independent prognostic factors for OS.

Conclusions

SIS was an independent prognostic factor for RFS and OS in pT2–4 resectable gastric cancer patients who underwent curative gastrectomy.
Disruption of DDX53 coding sequence has limited impact on iPSC-derived human NGN2 neurons
Authors: Faheem Muhammad , Deneault Eric , Alexandrova Roumiana , Rodrigues Deivid C. , Pellecchia Giovanna , Shum Carole , Zarrei Mehdi , Piekna Alina , Wei Wei , Howe Jennifer L. , Thiruvahindrapuram Bhooma , Lamoureux Sylvia , Ross P. Joel , Bradley Clarrisa A. , Ellis James , Scherer Stephen W.
Published: January 2023

Background

The X-linked PTCHD1 locus is strongly associated with autism spectrum disorder (ASD). Males who carry chromosome microdeletions of PTCHD1 antisense long non-coding RNA (PTCHD1-AS)/DEAD-box helicase 53 (DDX53) have ASD, or a sub-clinical form called Broader Autism Phenotype. If the deletion extends beyond PTCHD1-AS/DDX53 to the next gene, PTCHD1, which is protein-coding, the individuals typically have ASD and intellectual disability (ID). Three male siblings with a 90 kb deletion that affects only PTCHD1-AS (and not including DDX53) have ASD. We performed a functional analysis of DDX53 to examine its role in NGN2 neurons.

Methods

We used the clustered regularly interspaced short palindromic repeats (CRISPR) gene editing strategy to knock out DDX53 protein by inserting 3 termination codons (3TCs) into two different induced pluripotent stem cell (iPSC) lines. DDX53 CRISPR-edited iPSCs were differentiated into cortical excitatory neurons by Neurogenin 2 (NGN-2) directed differentiation. The functional differences of DDX53-3TC neurons compared to isogenic control neurons with molecular and electrophysiological approaches were assessed.

Results

Isogenic iPSC-derived control neurons exhibited low levels of DDX53 transcripts. Transcriptional analysis revealed the generation of excitatory cortical neurons and DDX53 protein was not detected in iPSC-derived control neurons by western blot. Control lines and DDX53-3TC neurons were active in the multi-electrode array, but no overt electrophysiological phenotype in either isogenic line was observed.

Conclusion

DDX53-3TC mutation does not alter NGN2 neuronal function in these experiments, suggesting that synaptic deficits causing ASD are unlikely in this cell type.
Triglyceride glucose index is associated with obstructive coronary artery disease in hypertensive patients
Authors: Pan Weili , Ren Yongkui , Yang Fan , Wang Minxian , Li Xinsheng , Yin Da
Published: January 2023

Background

Hypertension is a leading risk of coronary artery disease (CAD). Triglyceride glucose index (TyG) is a surrogate of insulin resistance (IR). Few studies explore the association between TyG and the incidence of obstructive CAD (OCAD) in hypertensive patients.

Methods

We retrospectively screened 1841 hypertensive subjects who were free of a history of CAD and underwent coronary computed tomography angiography (CCTA) because of chest pain. TyG index was calculated as ln (fasting TG [mg/dL] * fasting glucose [mg/dL]/2). The outcome of this research was OCAD, which was defined as the presence of diameter stenosis ≥ 50% in any of the four major epicardial coronary arteries detected on CCTA.

Results

A total of 310 (16.8%) patients developed obstructive CAD. The restricted cubic spline (RCS) analysis showed a J-shaped relationship between TyG and OCAD and the OR for OCAD increased as the TyG rose over 8.61 (OR perSD) 1.64, 95% CI 1.13–2.54, p = 0.008). After full adjustments for confounding covariates, patients with TyG index in tertile 3 (T3) had 2.12 times (95% CI 1.80 to 3.81) and in T2 had 2.01 times (95% CI 1.40 to 2.88) as high as the risk of OCAD compared with patients in T1 (p for trend = 0.001). When regarding TyG as a continuous variable, 1-SD increase elevated 49% (OR (95%CI), 1.49 (1.30–1.74)) risk of obstructive CAD (p = 0.007). This positive effect was still consistent across the subgroups (p for interaction > 0.05).

Conclusion

TyG index was associated with the incidence of obstructive CAD in hypertensive patients.
Optimizing the role of ‘lead mothers’ in seasonal malaria chemoprevention (SMC) campaigns: formative research in Kano State, northern Nigeria
Authors: Okereke Ekechi , Smith Helen , Oguoma Chibuzo , Oresanya Olusola , Maxwell Kolawole , Anikwe Chinedu , Osuji Lawrence Chijioke , Ogazi Obianuju , Musa Jamila , Rajab Ashiru , Shekarau Emmanuel , Okoh Festus , Viganò Erica , Donovan Laura , Ward Charlotte , Baker Kevin
Published: January 2023

Background

Seasonal malaria chemoprevention (SMC) is a safe and effective intervention for preventing malaria in children under 5 years of age. Lead mothers are community health volunteers that help caregivers comply with monthly administration of anti-malarial drugs during SMC campaigns. The lead mother approach is used in several SMC implementing states across Nigeria, but there is lack of evidence about their roles and how effective they are. This study sought to better understand the current role of lead mothers, identify areas for improvement and ways to optimize the role of lead mothers during SMC campaigns.

Methods

This paper reports the formative phase of a three-phased intervention development study. The formative phase involved semi-structured interviews with stakeholders from national, state, local government and community levels (n = 20). Thematic analysis was used to identify key themes, forming the basis of a subsequent co-design workshop with stakeholders routinely involved in SMC campaigns.

Results

The findings of the formative phase converged around four overarching themes: skills and attributes required of lead mothers; factors that affect lead mother’s roles; how lead mothers interact with Community Health Influencers Promoters Services (CHIPS) agents and re-imagining the role of lead mothers during SMC campaigns.

Conclusion

This formative work in Kano state indicates that through their strong connection to communities and unique relationship with caregivers, lead mothers can and do influence caregivers to adopt healthy behaviours during SMC campaigns. However, there is room for improvement in how they are recruited, trained and supervised. There is need to improve lead mothers’ knowledge and skills through adequate training and supporting materials, so they can deliver targeted health messages to caregivers. Sustainability of the lead mother approach is at risk if policymakers do not find a way of transitioning their role into the existing community health worker infrastructure, for example by using CHIPs agents, and ensuring less reliance on external donor support.
Addressing systemic problems with exposure assessments to protect the public’s health
Authors: Vandenberg Laura N. , Rayasam Swati D. G. , Axelrad Daniel A. , Bennett Deborah H. , Brown Phil , Carignan Courtney C. , Chartres Nicholas , Diamond Miriam L. , Joglekar Rashmi , Shamasunder Bhavna , Shrader-Frechette Kristin , Subra Wilma A. , Zarker Ken , Woodruff Tracey J.
Published: January 2023

Background

Understanding, characterizing, and quantifying human exposures to environmental chemicals is critical to protect public health. Exposure assessments are key to determining risks to the general population and for specific subpopulations given that exposures differ between groups. Exposure data are also important for understanding where interventions, including public policies, should be targeted and the extent to which interventions have been successful. In this review, we aim to show how inadequacies in exposure assessments conducted by polluting industries or regulatory agencies have led to downplaying or disregarding exposure concerns raised by communities; that underestimates of exposure can lead regulatory agencies to conclude that unacceptable risks are, instead, acceptable, allowing pollutants to go unregulated; and that researchers, risk assessors, and policy makers need to better understand the issues that have affected exposure assessments and how appropriate use of exposure data can contribute to health-protective decisions.

Methods

We describe current approaches used by regulatory agencies to estimate human exposures to environmental chemicals, including approaches to address limitations in exposure data. We then illustrate how some exposure assessments have been used to reach flawed conclusions about environmental chemicals and make recommendations for improvements.

Results

Exposure data are important for communities, public health advocates, scientists, policy makers, and other groups to understand the extent of environmental exposures in diverse populations. We identify four areas where exposure assessments need to be improved due to systemic sources of error or uncertainty in exposure assessments and illustrate these areas with examples. These include: (1) an inability of regulatory agencies to keep pace with the increasing number of chemicals registered for use or assess their exposures, as well as complications added by use of ‘confidential business information’ which reduce available exposure data; (2) the failure to keep assessments up-to-date; (3) how inadequate assumptions about human behaviors and co-exposures contribute to underestimates of exposure; and (4) that insufficient models of toxicokinetics similarly affect exposure estimates.

Conclusion

We identified key issues that impact capacity to conduct scientifically robust exposure assessments. These issues must be addressed with scientific or policy approaches to improve estimates of exposure and protect public health.
Overcoming multidrug-resistant lung cancer by mitochondrial-associated ATP inhibition using nanodrugs
Authors: Park Jun-Young , Lee Gyu-Ho , Yoo Kwai Han , Khang Dongwoo
Published: January 2023

Despite the development of therapeutic modalities to treat cancer, multidrug resistance (MDR) and incomplete destruction of deeply embedded lung tumors remain long-standing problems responsible for tumor recurrence and low survival rates. Therefore, developing therapeutic approaches to treat MDR tumors is necessary. In this study, nanodrugs with enhanced intracellular drug internalization were identified by the covalent bonding of carbon nanotubes of a specific nano size and doxorubicin (DOX). In addition, carbon nanotube conjugated DOX (CNT-DOX) sustained in the intracellular environment in multidrug-resistant tumor cells for a long time causes mitochondrial damage, suppresses ATP production, and results in the effective therapeutic effect of drug-resistant tumors. This study identified that H69AR lung cancer cells, an adriamycin (DOX) drug-resistant tumor cell line, did not activate drug resistance function on designed nano-anticancer drugs with a specific nano size. In summary, this study identified that the specific size of the nanodrug in combination with DOX overcame multidrug-resistant tumors by inducing selective accumulation in tumor cells and inhibiting ATP by mitochondrial damage.
Cloning and functional analysis of the molting gene CYP302A1 of Daphnia sinensis
Authors: Qi Huiying , Cao Huijuan , Zhao Yajie , Cao Yaqin , Jin Qide , Wang Yeping , Zhang Kun , Deng Daogui
Published: January 2023

Background

Molting is an important physiological process in the growth and development of arthropoda, which is mainly regulated by juvenile hormone and ecdysone. CYP302A1 is a key enzyme which plays a critical role in the synthesis of ecdysone in insects, but it has not been identified in cladocera.

Results

The CYP302Al gene of Daphnia sinensis was cloned and its function was analyzed in this paper. The CYP302Al gene of D. sinensis was 5926 bp in full-length, with an open reading frame (ORF) of 1596 bp that encoded 531 amino acids (aa), a molecular weight of 60.82 kDa and an isoelectric point of 9.29. The amino acid sequence analysis revealed that there were five characteristic conserved regions of cytochrome P450 family (namely helix-C, helix-K, helix-I, PERF and heme-binding). In dsRNA mediated experiment, the expression level of CYP302A1 gene decreased significantly (knock-down of 56.22%) in the 5% Escherichia coli concentration treatment. In addition, the expression levels of EcR and USP and HR3 genes in the downstream were also significantly decreased, whereas that of FTZ-f1 gene increased significantly. In the 5% E. coli treatment, the molting time at maturity of D. sinensis prolonged, and the development of embryos in the incubation capsule appeared abnormal or disintegrated. The whole-mount in situ hybridization showed that the CYP302A1 gene of D. sinensis had six expression sites before RNA interference (RNAi), which located in the first antennal ganglion, ovary, cecae, olfactory hair, thoracic limb and tail spine. However, the expression signal of the CYP302A1 gene of D. sinensis disappeared in the first antennal ganglion and obviously attenuated in the ovary after RNAi.

Conclusion

The CYP302A1 gene played an important role in the ecdysone synthesis pathway of D. sinensis, and the knock-down of the gene affected the molting and reproduction of D. sinensis.
Testing and evaluation of lower limb prosthesis prototypes in people with a transfemoral amputation: a scoping review on research protocols
Authors: Kooiman Vera G. M. , van Staveren Eline S. , Leijendekkers Ruud A. , Buurke Jaap H. , Verdonschot Nico , Prinsen Erik C. , Weerdesteyn Vivian
Published: January 2023

Background

When developing new lower limb prostheses, prototypes are tested to obtain insights into the performance. However, large variations between research protocols may complicate establishing the potential added value of newly developed prototypes over other prostheses.

Objective

This review aims at identifying participant characteristics, research protocols, reference values, aims, and corresponding outcome measures used during prosthesis prototype testing on people with a transfemoral amputation.

Methods

A systematic search was done on PubMed and Scopus from 2000 to December 2020. Articles were included if testing was done on adults with transfemoral or knee disarticulation amputation; testing involved walking with a non-commercially available prototype leg prosthesis consisting of at least a knee component; and included evaluations of the participants’ functioning with the prosthesis prototype.

Results

From the initial search of 2027 articles, 48 articles were included in this review. 20 studies were single-subject studies and 4 studies included a cohort of 10 or more persons with a transfemoral amputation. Only 5 articles reported all the pre-defined participant characteristics that were deemed relevant. The familiarization time with the prosthesis prototype prior to testing ranged from 5 to 10 min to 3 months; in 25% of the articles did not mention the extent of the familiarization period. Mobility was most often mentioned as the development or testing aim. A total of 270 outcome measures were identified, kinetic/kinematic gait parameters were most often reported. The majority of outcome measures corresponded to the mobility aim. For 48% of the stated development aims and 4% of the testing aims, no corresponding outcome measure could be assigned. Results indicated large inconsistencies in research protocols and outcome measures used to validate pre-determined aims.

Conclusions

The large variation in prosthesis prototype testing and reporting calls for the development of a core set of reported participant characteristics, testing protocols, and specific and well-founded outcome measures, tailored to the various aims and development phases. The use of such a core set can give greater insights into progress of developments and determine which developments have additional benefits over the state-of-the-art. This review may contribute as initial input towards the development of such a core set.
RETRACTED ARTICLE: Randomized controlled trial for selective preventive transdiagnostic intervention for adolescents at risk for emotional disorders
Authors: Vivas-Fernandez Manuel , Garcia-Lopez Luis-Joaquin , Piqueras Jose A. , Muela-Martinez Jose-Antonio , Canals-Sans Josefa , Espinosa-Fernandez Lourdes , Jimenez-Vazquez David , Diaz-Castela Maria del Mar , Morales-Hidalgo Paula , Rivera Maria , Ehrenreich-May Jill
Published: January 2023

Significant evidence does exist on the effectiveness of transdiagnostic interventions to improve emotional problems in clinical populations, and their application as universal and indicated prevention programs. However, no randomized controlled trials (RCT) studying selective transdiagnostic prevention intervention have been published. This is the first known RCT to evaluate the efficacy/effectiveness of an evidence-based selective prevention transdiagnostic program for emotional problems in adolescents. The impact of three different interventions was evaluated: (1) PROCARE (Preventive transdiagnostic intervention for Adolescents at Risk for Emotional disorders), which is a group-based, online-delivered, abbreviated version of the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders in Adolescents (UP-A), along with adding a booster session, to reduce risk of onset of anxiety and depression, (2) PROCARE + , which includes the PROCARE protocol along with personalized add-on modules tailored to match adolescents’ risk factors, and (3) an active control condition (ACC) based on emotional psychoeducation. In total, 286 adolescents (53.3% girls) evidencing high risk and low protective factors were randomized and allocated to PROCARE, PROCARE + or ACC. Self- and parent-reported measures were taken at baseline, as well as after the intervention, a 6-month follow-up was carried out, together with a 1-month follow-up after the booster session. Differences between conditions were significant on most of the outcome measures, with superior effect sizes for PROCARE +. Interventions were excellent in terms of acceptability, with good satisfaction rates. Tailored selective transdiagnostic interventions focused on mitigating risk factors and promoting protective factors in vulnerable adolescents are promising.
Periradicular repair after single- and two-visit root canal treatments using ultrasonic irrigant activation and calcium hydroxide dressing of teeth with apical periodontitis: study protocol for randomized controlled trials
Authors: Almeida Gustavo M. , Carvalho Vitor Hugo M. , Silva Érika B. P. , Cançado Marco Antonio F. , Barroso Leonardo S. , Queiroz Erica L. , An Tien Li , Ribeiro Ana Paula D. , Carvalho-Junior Jacy R. , Leite André F.
Published: January 2023

Background

In certain clinical situations, root canal treatment in teeth with apical periodontitis is performed in multiple visits, with the use of intracanal dressing between visits, aiming to reduce microorganisms and their by-products of the root canal system prior to filling. However, in recent years, discussions have been growing about the real need for the use of intracanal dressing in these cases. The use of ultrasonic activation of the auxiliary chemical substance has increased the potential for decontamination promoted during the chemomechanical preparation of the root canal. Thus, this study is designed to explore whether the use of intracanal dressing between visits during endodontic treatment favors periradicular repair in teeth with apical periodontitis.

Methods

This is a randomized, prospective, double-blinded, controlled clinical trial designed to evaluate 3 distinct clinical approaches used during endodontic therapy: group 1—root canal treatment in a single visit (RCT-SV); group 2—root canal treatment in two visits with intracanal dressing (RCT-TVWD); and group 3—root canal treatment in two visits without intracanal dressing (RCT-TVWOD). A total of 150 adult patients aged 18 to 60, with at least one tooth diagnosed with asymptomatic apical periodontitis and periradicular lesion (confirmed with a cone beam computed tomography (CBCT)), will be randomized and will undergo one of the types of clinical approaches during endodontic therapy. Patients’ postoperative pain levels will also be recorded in periods of 24, 48, and 72 h and 7 days. Subsequently, clinical findings and long-term follow-up evaluations, with periradicular repair, will be performed at 6 and 12 months by intraoral periapical radiograph (IOPAR) and CBCT at the 24-month follow-up.

Discussion

This study will evaluate the periradicular repair of mandibular molar teeth with apical periodontitis, providing information about the efficacy, benefits, and safety of performing the endodontic treatment in a single and two visits, with and without the use of calcium hydroxide dressing. All endodontic therapy procedures will be performed under a dental operating microscope and using ultrasonic activation of auxiliary chemical substances. These results may contribute to changes in the clinical approaches adopted during endodontic therapy of teeth with apical periodontitis and reveal the potential of complementary approaches that aim to enhance the decontamination of the root canal system during the preparation stage.

Trial registration

ClinicalTrials.gov NCT05256667. Registered on 24 February 2022
A novel stop-gain pathogenic variant in the KCNQ1 gene causing long QT syndrome 1
Authors: Kalayinia Samira , Dalili Mohammad , Pourirahim Maryam , Maleki Majid , Mahdieh Nejat
Published: January 2023

Background

Inherited primary arrhythmias, such as long QT (LQT) syndromes, are electrical abnormalities of the heart mainly due to variants in 3 genes. We herein describe a novel stop-gain pathogenic variant in the KCNQ1 gene in an Iranian child with LQT syndrome 1.

Methods

The patient and his family underwent clinical evaluation, electrocardiographic Holter monitoring, and whole-exome sequencing. Sanger sequencing and segregation analysis were used to confirm the variant in the patient and his family, respectively. The pathogenicity of the variant was checked via an in silico analysis.

Results

The proband suffered from bradycardia and had experienced syncope without stress. The corrected QT interval was 470 ms (the Schwartz score ≥ 3.5), and the Holter monitoring showed sinus rhythm, infrequent premature atrial contractions, and a prolonged QT interval in some leads. Whole-exome and Sanger sequencing showed c.968G > A in 3 affected family members. According to the American College of Medical Genetics and Genomics criteria, c.968G > A was classified as a pathogenic variant.

Conclusions

The KCNQ1 gene is the main cause of LQT syndromes in our population. The common genes of LQT syndromes should be studied in our country’s different ethnicities to determine the exact role of these genes in these subpopulations.
Phosphate, calcium, and vitamin D signaling, transport, and metabolism in the endometria of cyclic ewes
Authors: Stenhouse Claire , Newton Makenzie G. , Halloran Katherine M. , Moses Robyn M. , Sah Nirvay , Suva Larry J. , Bazer Fuller W.
Published: January 2023

Background

Recent evidence suggests important roles for progesterone (P4) and interferon tau in the regulation of calcium, phosphate, and vitamin D signaling in the uteri of pregnant sheep. However, the effects of P4 and estradiol (E2), with respect to the expression of their receptors PGR and ESR1, respectively, in uterine epithelia on mineral signaling during the estrous cycle has not been investigated. Estrous cycles of mature Suffolk ewes were synchronized, prostaglandin F2α was administered, and ewes were observed for estrus (designated as Day 0) in the presence of vasectomized rams. On Days 1, 9, or 14 of the estrous cycle, hysterectomies were performed.

Results

25-hydroxyvitamin D was more abundant in plasma from ewes on Day 14 than Day 1 (P < 0.05). Expression of fibroblast growth factor receptor 2 (FGFR2), a disintegrin and metalloprotease 17 (ADAM17), and parathyroid hormone-related protein (PTHrP) mRNAs was greater in endometria on Day 9 compared to Days 1 and 14 (P < 0.01). Similarly, expression of transient receptor potential cation channel subfamily V member 6 (TRPV6) mRNA was greater in endometria on Day 9 than Day 1 (P < 0.05). ATPase plasma membrane Ca2+ transporting 4 (ATP2B4) and S100 calcium binding protein G (S100G) mRNA expression was greater in endometria on Day 14 than on Days 1 and 9 (P < 0.01). In contrast, endometrial expression of vitamin D receptor (VDR) mRNA was lower on Days 9 and 14 than Day 1 (P < 0.01). Expression of klotho (KL) (P < 0.05) and cytochrome P450 family 24 subfamily A member 1 (CYP24) (P < 0.01) mRNAs was lower on Day 14 than Days 1 and 9. ADAM17, FGF23, CYP2R1, CYP27B1, KL, and VDR proteins immunolocalized to the uterine myometrium, blood vessels, and uterine luminal (LE), superficial glandular (sGE), and glandular (GE) epithelia. S100A9 protein was weakly expressed in the uterine myometrium, LE, sGE, and GE. Immunoreactivity of CYP2R1 and KL proteins in uterine LE and sGE was less on Day 1 than on Days 9 and 14. In contrast, S100G protein was expressed exclusively by GE, and immunoreactive S100G protein was less on Day 9. S100A12 protein localized to stromal cells of the uterine stratum spongiosum and blood vessels, but not by uterine epithelial cells.

Conclusion

Collectively, these results implicate E2, P4, and PGR in the regulation of phosphate, calcium, and vitamin D signaling in cyclic ewes.
Immune-related gene index predicts metastasis for prostate cancer patients undergoing radical radiotherapy
Authors: Feng Dechao , Zhu Weizhen , Shi Xu , Wang Zhihong , Wei Wuran , Wei Qiang , Yang Lu , Han Ping
Published: January 2023

In this study, we established a novel immunologic gene prognostic index (IGPI) to predict metastasis and provided new insights into tumor immune microenvironment (TIME) for PCa patients receiving radical radiotherapy. GBP2 and IGF1 were independent factors associated with metastasis-free survival. IGPI score was calculated based on GBP2 and IGF1 and this score was an independent risk factor for PCa patients undergoing radical radiotherapy. Patients with higher IGPI score were at higher risk of metastasis and biochemical recurrence, which were externally validated in the TCGA database and other GEO datasets. IGPI score had demonstrated moderate diagnostic ability of radiation resistance (AUC: 0.889). This score increased with the augment of Gleason score and T stage, as well as biochemical recurrence. Using EPIC, ESTIMATE and immunophenoscore (IPS) algorithms, cancer associated fibroblasts (CAFs), macrophages, stromal score, and estimate score were significantly higher in patients with metastasis group compared to their counterpart. Besides, for CAFs, macrophages, stromal score, and estimate score, patients with higher scores were at higher risk of metastasis, and the HRs were 3.65, 4.01, 4.27, and 3.78, respectively. IGPI score was highly positively associated with stromal score (coefficient: 0.39), immune score (coefficient: 0.43), estimate score (coefficient: 0.45), CAFs (coefficient: 0.42) and macrophages (coefficient: 0.42), while showing the opposite relationship with tumor purity (coefficient: − 0.45). In conclusion, we found that IGPI based on GBP2 and IGF1 might serve as a biomarker predicting metastasis for PCa patients. Besides, the current data further highlight the importance of CAFs in the metastatic process of PCa.
A framework for the targeted recruitment of crop-beneficial soil taxa based on network analysis of metagenomics data
Authors: Berihu Maria , Somera Tracey S. , Malik Assaf , Medina Shlomit , Piombo Edoardo , Tal Ofir , Cohen Matan , Ginatt Alon , Ofek-Lalzar Maya , Doron-Faigenboim Adi , Mazzola Mark , Freilich Shiri
Published: January 2023

Background

The design of ecologically sustainable and plant-beneficial soil systems is a key goal in actively manipulating root-associated microbiomes. Community engineering efforts commonly seek to harness the potential of the indigenous microbiome through substrate-mediated recruitment of beneficial members. In most sustainable practices, microbial recruitment mechanisms rely on the application of complex organic mixtures where the resources/metabolites that act as direct stimulants of beneficial groups are not characterized. Outcomes of such indirect amendments are unpredictable regarding engineering the microbiome and achieving a plant-beneficial environment.

Results

This study applied network analysis of metagenomics data to explore amendment-derived transformations in the soil microbiome, which lead to the suppression of pathogens affecting apple root systems. Shotgun metagenomic analysis was conducted with data from ‘sick’ vs ‘healthy/recovered’ rhizosphere soil microbiomes. The data was then converted into community-level metabolic networks. Simulations examined the functional contribution of treatment-associated taxonomic groups and linked them with specific amendment-induced metabolites. This analysis enabled the selection of specific metabolites that were predicted to amplify or diminish the abundance of targeted microbes functional in the healthy soil system. Many of these predictions were corroborated by experimental evidence from the literature. The potential of two of these metabolites (dopamine and vitamin B12) to either stimulate or suppress targeted microbial groups was evaluated in a follow-up set of soil microcosm experiments. The results corroborated the stimulant’s potential (but not the suppressor) to act as a modulator of plant beneficial bacteria, paving the way for future development of knowledge-based (rather than trial and error) metabolic-defined amendments. Our pipeline for generating predictions for the selective targeting of microbial groups based on processing assembled and annotated metagenomics data is available at https://github.com/ot483/NetCom2.

Conclusions

This research demonstrates how genomic-based algorithms can be used to formulate testable hypotheses for strategically engineering the rhizosphere microbiome by identifying specific compounds, which may act as selective modulators of microbial communities. Applying this framework to reduce unpredictable elements in amendment-based solutions promotes the development of ecologically-sound methods for re-establishing a functional microbiome in agro and other ecosystems.
Expanded catalogue of metagenome-assembled genomes reveals resistome characteristics and athletic performance-associated microbes in horse
Authors: Li Cunyuan , Li Xiaoyue , Guo Rongjun , Ni Wei , Liu Kaiping , Liu Zhuang , Dai Jihong , Xu Yueren , Abduriyim Shamshidin , Wu Zhuangyuan , Zeng Yaqi , Lei Bingbing , Zhang Yunfeng , Wang Yue , Zeng Weibin , Zhang Qiang , Chen Chuangfu , Qiao Jun , Liu Chen , Hu Shengwei
Published: January 2023

Background

As a domesticated species vital to humans, horses are raised worldwide as a source of mechanical energy for sports, leisure, food production, and transportation. The gut microbiota plays an important role in the health, diseases, athletic performance, and behaviour of horses.

Results

Here, using approximately 2.2 Tb of metagenomic sequencing data from gut samples from 242 horses, including 110 samples from the caecum and 132 samples from the rectum (faeces), we assembled 4142 microbial metagenome-assembled genomes (MAG), 4015 (96.93%) of which appear to correspond to new species. From long-read data, we successfully assembled 13 circular whole-chromosome bacterial genomes representing novel species. The MAG contained over 313,568 predicted carbohydrate-active enzymes (CAZy), over 59.77% of which had low similarity match in CAZy public databases. High abundance and diversity of antibiotic resistance genes (ARG) were identified in the MAG, likely showing the wide use of antibiotics in the management of horse. The abundances of at least 36 MAG (e.g. MAG belonging toLachnospiraceae,Oscillospiraceae, andRuminococcus) were higher in racehorses than in nonracehorses. These MAG enriched in racehorses contained every gene in a major pathway for producing acetate and butyrate by fibre fermentation, presenting potential for greater amount of short-chain fatty acids available to fuel athletic performance.

Conclusion

Overall, we assembled 4142 MAG from short- and long-read sequence data in the horse gut. Our dataset represents an exhaustive microbial genome catalogue for the horse gut microbiome and provides a valuable resource for discovery of performance-enhancing microbes and studies of horse gut microbiome.
A methodology for the public health surveillance and epidemiologic analysis of outdoor falls that require an emergency medical services response
Authors: Rundle Andrew G. , Crowe Remle P. , Wang Henry E. , Lo Alexander X.
Published: January 2023

Background

Falls are a common cause of injury with significantly associated medical costs yet public health surveillance of injuries from falls is underdeveloped. In addition, the epidemiologic understanding of outdoor falls, which have been reported to account for 47% of all injurious falls, is scant. Here we present methods to use emergency medical services (EMS) data as a public health surveillance tool for fall injuries, including those that occur secondary to syncope and heat illness, with a focus on the scope and epidemiology of outdoor fall injuries.

Methods

Using the 2019 National Emergency Medical Services Information System (NEMSIS) data, we developed an approach to identify EMS encounters for fall injuries, syncope and heat illness. NEMSIS variables used in our algorithm included the EMS respondent’s impression of the encounter, the reported major symptoms and the cause of injury. With these data we identified injuries from falls and, using the NEMSIS data on the location of the encounter, we identified fall injuries as occurring indoors or outdoors. We present the descriptive epidemiology of the identified patients.

Results

There were 1,854,909 injuries from falls that required an EMS response identified in the NEMSIS data, with 4% of those injuries secondary to episodes of syncope (n = 73,126) and heat illness. Sufficient data were available from 94% of injurious falls that they could be assigned to indoor or outdoor locations, with 9% of these fall injuries occurring outdoors. Among fall injuries identified as occurring outdoors, 85% occurred on streets and sidewalks. Patient age was the primary sociodemographic characteristic that varied by location of the injurious fall. Sixty-six percent of fall injuries that occurred indoors were among those age 65 years or older, while this figure was 34% for fall injuries occurring outdoors on a street or sidewalk.

Conclusion

The occurrence of outdoor fall injuries identified in the NEMSIS data were substantially lower than reported in other data sets. However, numerically fall injuries occurring outdoors represent a substantial public health burden. The strengths and weaknesses of using this approach for routine public health surveillance of injuries from falls, syncope and heat illness are discussed.
Spatial distribution of poverty in Pakistan: an asset-based approach
Authors: Ullah Kifayat , Chishti Muhammad Zubair
Published: January 2023

The main objective of this study is to construct a valid and reliable asset index at household level by using NSER-BISP data in order to compute asset poverty for provinces, districts, and tehsils of the Pakistan. An asset index may be better measure than current income or expenditure for gauging household’s long-term capacity for buying goods and services and its potential resilience to economic shocks. The study employs multiple correspondence analysis (MCA) to construct asset index contrary to principal component analysis (PCA), as MCA provides us weights and contributions of each dimension of binary variable separately. The average MCA score is showing the level of asset-based poverty wherein higher values of index are representing higher level of poverty. The findings indicate that incidence of asset-based poverty is differently observed across provinces and within provinces through disaggregation of the MCA score at district and tehsil levels. By and large, the poorest districts of Pakistan are belonging to Baluchistan (i.e., Sherani, Kohlu, Chaghi, and Dera Bugti) and Sindh (i.e., Badin, Umerkot, Tando Muhammad Khan, and Tharparker) provinces; however, districts of Punjab (i.e., Lahore, Rawalpindi, and Gujranwala) province are found relatively lower asset-based poverty. Further, the analysis highlights the prevalence of asset-based poverty at tehsils level as well where again the tehsils of Baluchistan and Sindh provinces are bearing the highest asset-based poverty. Furthermore, the study also contributes by visualizing the prevalence of geographical asset-based poverty at district level for all four provinces of Pakistan by GIS mapping.
Perinatal mental health in medical school curricula: a national scoping survey of British universities and student psychiatry societies
Authors: King Jacob D. , Crowley Grace , El-Maraghy Manal , Davis William , Jauhari Archana , Wilson-Jones Charlotte
Published: January 2023

Aims and method

With increasing recognition of the prevalence and impact of perinatal mental health (PMH) disorders comes a responsibility to ensure that tomorrow's doctors can support families during the perinatal period. Online surveys seeking information about the inclusion of PMH education in undergraduate curricula were sent to psychiatry curriculum leads and student psychiatry societies from each university medical school in the UK between April and September 2021.

Results

Responses were received from 32/35 (91.4%) medical schools. Two-thirds reported specific inclusion of PMH content in the core curriculum, typically integrated into general adult psychiatry or obstetric teaching. Students at the remaining schools were all likely to be examined on the topic or see perinatal cases during at least one clinical attachment.

Clinical implications

PMH education offers an opportunity for collaboration between psychiatry and other disciplines. Future work looking at educational case examples with objective outcomes would be valuable.
Intranasal Carbetocin Reduces Hyperphagia, Anxiousness, and Distress in Prader-Willi Syndrome: CARE-PWS Phase 3 Trial
Authors: Roof Elizabeth , Deal Cheri L , McCandless Shawn E , Cowan Ronald L , Miller Jennifer L , Hamilton Jill K , Roeder Elizabeth R , McCormack Shana E , Roshan Lal Tamanna R , Abdul-Latif Hussein D , Haqq Andrea M , Obrynba Kathryn S , Torchen Laura C , Vidmar Alaina P , Viskochil David H , Chanoine Jean-Pierre , Lam Carol K L , Pierce Melinda J , Williams Laurel L , Bird Lynne M , Butler Merlin G , Jensen Diane E , Myers Susan E , Oatman Oliver J , Baskaran Charumathi , Chalmers Laura J , Fu Cary , Alos Nathalie , McLean Scott D , Shah Ajay , Whitman Barbara Y , Blumenstein Brent A , Leonard Sarah F , Ernest Jessica P , Cormier Joseph W , Cotter Sara P , Ryman Davis C
Published: January 2023

Context

Prader-Willi syndrome (PWS) is a rare genetic disorder characterized by endocrine and neuropsychiatric problems including hyperphagia, anxiousness, and distress. Intranasal carbetocin, an oxytocin analog, was investigated as a selective oxytocin replacement therapy.

Objective

To evaluate safety and efficacy of intranasal carbetocin in PWS.

Design

Randomized, double-blind, placebo-controlled phase 3 trial with long-term follow-up.

Setting

Twenty-four ambulatory clinics at academic medical centers.

Participants

A total of 130 participants with PWS aged 7 to 18 years.

Interventions

Participants were randomized to 9.6 mg/dose carbetocin, 3.2 mg/dose carbetocin, or placebo 3 times daily during an 8-week placebo-controlled period (PCP). During a subsequent 56-week long-term follow-up period, placebo participants were randomly assigned to 9.6 mg or 3.2 mg carbetocin, with carbetocin participants continuing at their previous dose.

Main outcome measures

Primary endpoints assessed change in hyperphagia (Hyperphagia Questionnaire for Clinical Trials [HQ-CT]) and obsessive-compulsive symptoms (Children's Yale-Brown Obsessive-Compulsive Scale [CY-BOCS]) during the PCP for 9.6 mg vs placebo, and the first secondary endpoints assessed these same outcomes for 3.2 mg vs placebo. Additional secondary endpoints included assessments of anxiousness and distress behaviors (PWS Anxiousness and Distress Behaviors Questionnaire [PADQ]) and clinical global impression of change (CGI-C).

Results

Because of onset of the COVID-19 pandemic, enrollment was stopped prematurely. The primary endpoints showed numeric improvements in both HQ-CT and CY-BOCS which were not statistically significant; however, the 3.2-mg arm showed nominally significant improvements in HQ-CT, PADQ, and CGI-C scores vs placebo. Improvements were sustained in the long-term follow-up period. The most common adverse event during the PCP was mild to moderate flushing.

Conclusions

Carbetocin was well tolerated, and the 3.2-mg dose was associated with clinically meaningful improvements in hyperphagia and anxiousness and distress behaviors in participants with PWS.

Clinical Trials Registration Number

NCT03649477
Hydrozoan sperm-specific SPKK motif-containing histone H2B variants stabilise chromatin with limited compaction
Authors: Török Anna , Browne Martin J. G. , Vilar Jordina C. , Patwal Indu , DuBuc Timothy Q. , Febrimarsa  , Atcheson Erwan , Frank Uri , Gornik Sebastian G. , Flaus Andrew
Published: January 2023

Many animals achieve sperm chromatin compaction and stabilisation by replacing canonical histones with sperm nuclear basic proteins (SNBPs) such as protamines during spermatogenesis. Hydrozoan cnidarians and echinoid sea urchins lack protamines and have evolved a distinctive family of sperm-specific histone H2Bs (spH2Bs) with extended N termini rich in SPK(K/R) motifs. Echinoid sperm packaging is regulated by spH2Bs. Their sperm is negatively buoyant and fertilises on the sea floor. Hydroid cnidarians undertake broadcast spawning but their sperm properties are poorly characterised. We show that Hydractinia echinata and H. symbiolongicarpus sperm chromatin possesses higher stability than somatic chromatin, with reduced accessibility to transposase Tn5 integration and to endonucleases in vitro. In contrast, nuclear dimensions are only moderately reduced in mature Hydractinia sperm. Ectopic expression of spH2B in the background of H2B.1 knockdown results in downregulation of global transcription and cell cycle arrest in embryos, without altering their nuclear density. Taken together, SPKK-containing spH2B variants act to stabilise chromatin and silence transcription in Hydractinia sperm with only limited chromatin compaction. We suggest that spH2Bs could contribute to sperm buoyancy as a reproductive adaptation.
Equating NHANES Monitor-Based Physical Activity to Self-Reported Methods to Enhance Ongoing Surveillance Efforts
Authors: WELK GREGORY J. , LAMOUREUX NICHOLAS R. , ZENG CHENGPENG , ZHU ZHENGYUAN , BERG EMILY , WOLFF-HUGHES DANA L. , TROIANO RICHARD P.
Published: January 2023

Purpose

Harmonization of assessment methods represents an ongoing challenge in physical activity research. Previous research has demonstrated the utility of calibration approaches to enhance agreement between measures of physical activity. The present study utilizes a calibration methodology to add behavioral context from the Global Physical Activity Questionnaire (GPAQ), an established report-based measure, to enhance interpretations of monitor-based data scored using the novel Monitor Independent Movement Summary (MIMS) methodology.

Methods

Matching data from the GPAQ and MIMS were obtained from adults (20–80 yr of age) assessed in the 2011–2014 National Health and Nutrition Examination Survey. After developing percentile curves for self-reported activity, a zero-inflated quantile regression model was developed to link MIMS to estimates of moderate to vigorous physical activity (MVPA) from the GPAQ.

Results

Cross-validation of the model showed that it closely approximated the probability of reporting MVPA across age and activity-level segments, supporting the accuracy of the zero-inflated model component. Validation of the quantile regression component directly corresponded to the 25%, 50%, and 75% values for both men and women, further supporting the model fit.

Conclusions

This study offers a method of improving activity surveillance by translating accelerometer signals into interpretable behavioral measures using nationally representative data. The model provides accurate estimates of minutes of MVPA at a population level but, because of the bias and error inherent in report-based measures of physical activity, is not suitable for converting or interpreting individual-level data. This study provides an important preliminary step in utilizing information from both device- and report-based methods to triangulate activity related outcomes; however additional measurement error modeling is needed to improve precision.