bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti‐shigellosis activity of the aqueous extract of garlic, clove and fenugreek
Authors: Amer Sara Adel , Abd El‐Rahman Hanaa Sayed Mohamed 
Published: April 2022

AbstractShigellosis causes severe diarrhea and, in some cases, death in children. In this study, we investigated the in vitro and in vivo anti‐shigellosis efficacy of some aqueous herbal extracts or their chosen mixtures, including fenugreek seed, black seed, clove, garlic, and ginger. The antibacterial potential was assessed by well diffusion and microdilution assays. The extracts' minimum inhibitory concentrations ranged from 0.39 to 12.5 mg/ml. The water extract of garlic and combinations of garlic with either fenugreek or clove extracts had the highest antibacterial efficacy, hence these extracts were chosen for the in vivo investigation. Rats were given aShigella dysenteriaeinoculum and then administrated two doses (100 and 200 mg/kg bw) of the selected herbal extracts or the antibiotic ciprofloxacin (20 mg/kg bw) to treat Shigellosis in vivo. The results showed that garlic and clove extract mixtures (G6, 200 mg/kg bw), garlic and fenugreek mixtures (G7 and G8, 100 and 200 mg/kg bw), and ciprofloxacin group (G9, 20 mg/kg bw) had the best anti‐Shigellosis efficacy. G7 (garlic and fenugreek mixtures (100 mg/kg bw) outperformed almost all other groups evaluated. This group had lower defecation frequency, lower stool‐Shigellaloudness, restored body weight, recovered hematological, and liver and kidney functions, besides exhibited no anatomical alterations in the colon tissue that were comparable to the uninfected group. As a result, in the treatment ofShigella, this extract combination may be suggested as a viable therapeutic alternative to antibiotics.
Mechanical properties and cellular content of leukocyte‐ and platelet‐rich fibrin membranes of patients on antithrombotic drugs
Authors: Ockerman Anna , Hendrickx Amber , Willekens Wouter , Fehervary Heleen , Vastmans Julie , Coucke Wim , Verhamme Peter , Politis Constantinus , Vanassche Thomas , Braem Annabel , Quirynen Marc , Jacobs Reinhilde 
Published: April 2022

AbstractIntroductionThe aim of this study was to examine the potential influence of antithrombotics on leukocyte‐ and platelet‐rich fibrin (L‐PRF) membranes.MethodsTensile tests and cell counts were performed with L‐PRF membranes originating from patients on anticoagulants and antiplatelets versus patients not taking antithrombotics.ResultsFor the tensile tests, 13 control patients, 12 on anticoagulants, and 10 on antiplatelets donated blood. Compared to controls, membranes from anticoagulated donors were weaker (strength 0.57 ± 0.24 MPa vs. 0.80 ± 0.27 MPa,p = .03) and could not be stretched as far (1.8 ± 0.3 vs. 2.1 ± 0.3 times the initial length,p = .01). For the cell counting, 23 control patients, 16 on anticoagulants, and 16 on antiplatelets donated blood. The percentage of platelets was ±50% in the three groups. The percentage of leukocytes was lower in the anticoagulant group compared with controls (69 ± 10% vs. 78 ± 8%,p = .04). However, because of the unknown error of method, it is questionable whether the statistical significance is meaningful. There was no difference between membranes from the control group and the group on antiplatelets.ConclusionOur results indicate that L‐PRF membranes originating from patients on anticoagulants are weaker, stretch less far, and contain less leukocytes than L‐PRF membranes of patients not taking these drugs.
True Orthophoto Generation Based on Unmanned Aerial Vehicle Images Using Reconstructed Edge Points
Authors: Ebrahimikia Mojdeh , Hosseininaveh Ali 
Published: April 2022

AbstractAfter considering state‐of‐the‐art algorithms, this paper presents a novel method for generating true orthophotos from unmanned aerial vehicle (UAV) images of urban areas. The procedure consists of four steps: 2D edge detection in building regions, 3D edge graph generation, digital surface model (DSM) modification and, finally, true orthophoto and orthomosaic generation. The main contribution of this paper is concerned with the first two steps, in which deep‐learning approaches are used to identify the structural edges of the buildings and the estimated 3D edge points are added to the point cloud for DSM modification. Running the proposed method as well as four state‐of‐the‐art methods on two different datasets demonstrates that the proposed method outperforms the existing orthophoto improvement methods by up to 50% in the first dataset and by 70% in the second dataset by reducing true orthophoto distortion in the structured edges of the buildings.
Water property rights in investor‐state contracts on extractive activities, affects water governance: An empirical assessment of 80 contracts in Africa and Asia
Authors: Bosch Hilmer J. , Gupta Joyeeta 
Published: April 2022

AbstractIn view of increasing globalization, the ongoing promotion of foreign direct investment and the lack of comparative literature on how water property rights are changing in the global South, this article asks: How have property rights in water evolved through investor‐State contracts on mineral, petroleum and land issues in Africa and Asia? We analyse 80 publicly available contracts—22 minerals, 40 petroleum and 18 land—of 34 African and 19 Asian countries. We find that: (i) in addition to a State's water law, water allocation is also implicitly governed by contracts and international investment treaties; (ii) States de facto privatize water by allocating quasi‐property rights through the granting of contracts to foreign international investors; (iii) such waters exploited by virtue of contracts reduce the ability of States to regulate water during the term of the contract especially as investors' water use is protected by bilateral investment treaties and potential compensation claims; and (iv) the need of the State to increasingly adaptively govern water as the impacts of climate change on water become more noticeable will be challenged by the long‐term quasi property rights granted by States to investors in such contracts.
Metabolic alkalosis in hemodialysis patients
Authors: Mudunuru S. Arvind , Navarrete Jose , O'Neill W. Charles 
Published: April 2022

AbstractBackground: Hemodialysis solutions typically contain a high alkali concentration designed to counter interdialytic acidosis, but this could result in persistent alkalosis in some patients. The prevalence and significance of persistent alkalosis were therefore examined at four outpatient centers over a 10‐year period. Methods: Alkalosis was defined as a pre‐dialysis serum [HCO3] ≥ 26 meq/L in >6 months of a 12‐month period and was persistent if present in a majority of months thereafter. Control patients had a serum [HCO3] of 19–23 meq/L > 6 of every 12 months. Standard, citrate‐containing dialysate was used in all patients without adjustment of bicarbonate concentration. Results: 444 of 1271 patients had alkalosis that persisted in 73. Compared to control patients, persistently alkalotic patients were older, but gender, race, starting weight, comorbidities, and mortality did not differ. Dialysis dose was 7% greater, protein catabolic rate was 11% lower, and interdialytic weight gain was 29% lower, all p < 0.001. Persistently alkalotic patients had double the incidence of cardiac arrhythmias (p = 0.07) and a 20% greater intradialytic blood pressure decrease (p < 0.001). Conclusions: Alkalosis is common in hemodialysis patients and can be persistent, likely due to decreased protein catabolic rate and increased dialysis dose, and may have detrimental cardiovascular effects.
Spectrum of diseases associated with pyoderma gangrenosum and correlation with effectiveness of therapy: New insights on the diagnosis and therapy of comorbid hidradenitis suppurativa
Authors: Fischer Alexander H. , Jourabchi Natanel , Khalifian Saami , Lazarus Gerald S. 
Published: April 2022

AbstractPyoderma gangrenosum (PG) has been linked to various underlying systemic diseases; many associations are based on case reports or small case series, including hidradenitis suppurativa. Literature examining systemic therapies according to underlying comorbid condition is limited. The study objective was to investigate comorbid diseases of PG and correlate disease associations with effectiveness of therapeutic interventions. Using Johns Hopkins Medical Institutions medical records, 220 patients had an ICD‐9 code of 686.01 for PG between 1 January 2006 and 30 June 2015, of whom 130 patients met rigorous inclusion/exclusion criteria for PG (non‐peristomal). The 130 PG patients in our study were 69% female, 58% Caucasian, and 35% African American. Documented comorbid conditions included inflammatory bowel disease (IBD; 35%), rheumatoid arthritis (RA; 12%), hidradenitis suppurativa (HS; 14%), and monoclonal gammopathy (12%). PG patients with HS versus without HS were more likely to be African‐American (83% vs. 28%; P < 0.001) and had an earlier mean age of PG onset (38 vs. 48 years; P = 0.02). Strikingly, 53% of female African‐American patients with PG onset prior to age 40 had comorbid HS. Comorbid inflammatory bowel disease was observed in 38% of PG patients with RA, 28% of PG patients with HS, and 27% of PG patients with monoclonal gammopathy. Of the 32 patients who received infliximab for active PG, complete ulcer healing was observed in 83% (5/6) of patients with comorbid HS versus 31% (8/26) of patients without HS (Fisher exact P = 0.03). Screening patients for associated systemic disease for multiple related illnesses is essential. Effectiveness of systemic therapy may depend upon the underlying systemic disease; hidradenitis suppurativa may be a specific example.
Phosphorylation and Stabilization of PD-L1 by CK2 Suppresses Dendritic Cell Function
Authors: Zhao Xixi , Wei Yongkun , Chu Yu-Yi , Li Yintao , Hsu Jung-Mao , Jiang Zhou , Liu Chunxiao , Hsu Jennifer L. , Chang Wei-Chao , Yang Riyao , Chan Li-Chuan , Qu Jingkun , Zhang Shuqun , Ying Haoqiang , Yu Dihua , Hung Mien-Chie 
Published: April 2022

Abstract

Targeting immune checkpoints such as programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) has transformed cancer treatment, with durable clinical responses across a wide range of tumor types. However, a high percentage of patients fail to respond to anti–PD-1/PD-L1 treatment. A greater understanding of PD-L1 regulation is critical to improving the clinical response rate of PD-1/PD-L1 blockade. Here, we demonstrate that PD-L1 is phosphorylated and stabilized by casein kinase 2 (CK2) in cancer and dendritic cells (DC). Phosphorylation of PD-L1 at Thr285 and Thr290 by CK2 disrupted PD-L1 binding with speckle-type POZ protein, an adaptor protein of the cullin 3 (CUL3) ubiquitin E3 ligase complex, protecting PD-L1 from CUL3-mediated proteasomal degradation. Inhibition of CK2 decreased PD-L1 protein levels by promoting its degradation and resulted in the release of CD80 from DC to reactivate T-cell function. In a syngeneic mouse model, combined treatment with a CK2 inhibitor and an antibody against T-cell immunoglobulin mucin-3 (Tim-3) suppressed tumor growth and prolonged survival. These findings uncover a mechanism by which PD-L1 is regulated and suggest a potential antitumor treatment option to activate DC function by blocking the CK2–PD-L1 pathway and inhibiting Tim-3.

Significance:
This work identifies a role for CK2 in immunosuppression by phosphorylation and stabilization of PD-L1, identifying CK2 inhibition as an immunotherapeutic approach for treating cancer.
Immune Determinants of the Association between Tumor Mutational Burden and Immunotherapy Response across Cancer Types
Authors: Sinha Neelam , Sinha Sanju , Valero Cristina , Schäffer Alejandro A. , Aldape Kenneth , Litchfield Kevin , Chan Timothy A. , Morris Luc G.T. , Ruppin Eytan 
Published: April 2022

Abstract

The FDA has recently approved a high tumor mutational burden (TMB-high) biomarker, defined by ≥10 mutations/Mb, for the treatment of solid tumors with pembrolizumab, an immune checkpoint inhibitor (ICI) that targets PD1. However, recent studies have shown that this TMB-high biomarker is only able to stratify ICI responders in a subset of cancer types, and the mechanisms underlying this observation have remained unknown. The tumor immune microenvironment (TME) may modulate the stratification power of TMB (termed TMB power), determining if it will be predictive of ICI response in a given cancer type. To systematically study this hypothesis, we inferred the levels of 31 immune-related factors characteristic of the TME of different cancer types in The Cancer Genome Atlas. Integration of this information with TMB and response data of 2,277 patients treated with anti-PD1 identified key immune factors that determine TMB power across 14 different cancer types. We find that high levels of M1 macrophages and low resting dendritic cells in the TME characterized cancer types with high TMB power. A model based on these two immune factors strongly predicted TMB power in a given cancer type during cross-validation and testing (Spearman Rho = 0.76 and 1, respectively). Using this model, we predicted the TMB power in nine additional cancer types, including rare cancers, for which TMB and ICI response data are not yet publicly available. Our analysis indicates that TMB-high may be highly predictive of ICI response in cervical squamous cell carcinoma, suggesting that such a study should be prioritized.

Significance:
This study uncovers immune-related factors that may modulate the relationship between high tumor mutational burden and ICI response, which can help prioritize cancer types for clinical trials.
Templated Insertions Are Associated Specifically with BRCA2 Deficiency and Overall Survival in Advanced Ovarian Cancer
Authors: Moore Grace , Majumdar Rahul , Powell Simon N. , Khan Atif J. , Weinhold Nils , Yin Shen , Higginson Daniel S. 
Published: April 2022

Abstract

Cancer cells defective in homologous recombination (HR) are responsive to DNA-crosslinking chemotherapies, PARP inhibitors, and inhibitors of polymerase theta (Pol θ), a key mediator of the backup pathway alternative end-joining. Such cancers include those with pathogenic biallelic alterations in core HR genes and another cohort of cases that exhibit sensitivity to the same agents and harbor genomic hallmarks of HR deficiency (HRD). These HRD signatures include a single-base substitution pattern, large rearrangements, characteristic tandem duplications, and small deletions. Here, we used what is now known about the backup pathway alternative end-joining (Alt-EJ) through the key factor Pol θ to design and test novel signatures of polymerase theta–mediated (TMEJ) repair. We generated two novel signatures; a signature composed of small deletions with microhomology and another consisting of small, templated insertions (TINS). We find that TINS consistent with TMEJ repair are highly specific to tumors with pathogenic biallelic mutations in BRCA2 and that high TINS genomic signature content in advanced ovarian cancers associate with overall survival following treatment with platinum agents. In addition, the combination of TINS with other HRD metrics significantly improves the association of platinum sensitivity with survival compared with current state-of-the-art signatures.

Implications:
Small, templated insertions indicative of theta-mediated end-joining likely can be used in conjunction with other HRD mutational signatures as a prognostic tool for patient response to therapies targeting HR deficiency.
Use of Ceftriaxone as a Predictor of Good Outcome in Stroke Patients: A Retrospective Chart Review
Authors: Dev Priya , Singh Varun Kumar , Kumar Anand , Chaurasia Rameshwar Nath , Singh Neelima Alka , Gautam Priyanka , Dhimani Neetu Rani , Mishra Vijaya Nath , Joshi Deepika , Pathak Abhishek 
Published: April 2022

Background: Whether ceftriaxone (CEFT) has any added advantage other than its antibiotics effect in stroke as a neuroprotective agent is not known, and this forms the base of this study. Purpose: We tried to assess the predictive role of the use of CEFT with respect to outcome in stroke patients. Methods: A retrospective chart review was conducted from a stroke registry over consecutive stroke patients admitted at a tertiary teaching institute from January 2017 to December 2018. Patients were categorized into three groups on the basis of antibiotics they received; patients without antibiotic treatment (NAB), piperacillin plus tazobactam treatment, and the CEFT treatment group. The outcome was assessed by the modified Rankin Scale at three months in good (0–3) and poor outcomes (4–6). Results: A total of 390 stroke patients were analyzed with ages ranging between 20 and 95 years and 151 of them were females. It was found that the severity at three months was significantly lower in those patients who were given CEFT antibiotic ( P = 0.04; OR = 0.626; 95% CI [0.396, 0.990]). Conclusion: Stroke patients in CEFT-treated group have a better outcome compared to piperacillin–tazobactam therapy or without antibiotics use at three months. This study indicates the possibility of an additional neuroprotective effect of CEFT apart from its antibacterial property.
Investigating treatment-effect modification by a continuous covariate in IPD meta-analysis: an approach using fractional polynomials
Authors: Sauerbrei Willi , Royston Patrick 
Published: April 2022

AbstractBackgroundIn clinical trials, there is considerable interest in investigating whether a treatment effect is similar in all patients, or that one or more prognostic variables indicate a differential response to treatment. To examine this, a continuous predictor is usually categorised into groups according to one or more cutpoints. Several weaknesses of categorization are well known. To avoid the disadvantages of cutpoints and to retain full information, it is preferable to keep continuous variables continuous in the analysis. To handle this issue, the Subpopulation Treatment Effect Pattern Plot (STEPP) was proposed about two decades ago, followed by the multivariable fractional polynomial interaction (MFPI) approach. Provided individual patient data (IPD) from several studies are available, it is possible to investigate for treatment heterogeneity with meta-analysis techniques. Meta-STEPP was recently proposed and in patients with primary breast cancer an interaction of estrogen receptors with chemotherapy was investigated in eight randomized controlled trials (RCTs).MethodsWe use data from eight randomized controlled trials in breast cancer to illustrate issues from two main tasks. The first task is to derive a treatment effect function (TEF), that is, a measure of the treatment effect on the continuous scale of the covariate in the individual studies. The second is to conduct a meta-analysis of the continuous TEFs from the eight studies by applying pointwise averaging to obtain a mean function. We denote the method metaTEF. To improve reporting of available data and all steps of the analysis we introduce a three-part profile called MethProf-MA.ResultsAlthough there are considerable differences between the studies (populations with large differences in prognosis, sample size, effective sample size, length of follow up, proportion of patients with very low estrogen receptor values) our results provide clear evidence of an interaction, irrespective of the choice of the FP function and random or fixed effect models.ConclusionsIn contrast to cutpoint-based analyses, metaTEF retains the full information from continuous covariates and avoids several critical issues when performing IPD meta-analyses of continuous effect modifiers in randomised trials. Early experience suggests it is a promising approach.Trial registrationNot applicable.
Balance recovery stepping responses during walking were not affected by a concurrent cognitive task among older adults
Authors: Paran Inbal , Nachmani Hadas , Salti Moti , Shelef Ilan , Melzer Itshak 
Published: April 2022

Abstract
Background
Most of older adults’ falls are related to inefficient balance recovery after an unexpected loss of balance, i.e., postural perturbation. Effective balance recovery responses are crucial to prevent falls. Due to the considerable consequences of lateral falls and the high incidence of falls when walking, this study aimed to examine the effect of a concurrent cognitive task on older adults’ balance recovery stepping abilities from unannounced lateral perturbations while walking. We also aimed to explore whether cognitive performance accuracy is affected by perturbed walking and between task trade-offs.

Methods
In a laboratory-based study, 20 older adults (> 70 years old) performed the following test conditions: (1) cognitive task while sitting; (2) perturbed walking; and (3) perturbed walking with a concurrent cognitive task. The cognitive task was serial numbers subtraction by seven. Single-step and multiple-step thresholds, highest perturbation achieved, 3D kinematic analysis of the first recovery step, and cognitive task performance accuracy were compared between single-task and dual-task conditions. Between task trade-offs were examined using dual-task cost (DTC).

Results
Single-step and multiple-step thresholds, number of recovery step trials, number of foot collision, multiple-step events and kinematic recovery step parameters were all similar in single-task and dual-task conditions. Cognitive performance was not significantly affected by dual-task conditions, however, different possible trade-offs between cognitive and postural performances were identified using DTC.

Conclusions
In situations where postural threat is substantial, such as unexpected balance loss during walking, balance recovery reactions were unaffected by concurrent cognitive load in older adults (i.e., posture first strategy).
The study was approved by the Helsinki Ethics Committee of Soroka University Medical Center in Beer-Sheva, Israel (ClinicalTrials.gov Registration number NCT04455607, ID Numbers: Sor 396–16 CTIL; 02/07/2020).