bluuebunny/crossref_metadata_2025 huggingface dataset:
“There’s absolutely no downside to this, I mean, except community opposition:” A qualitative study of the acceptability of vending machines for harm reduction
Authors: Stewart Rebecca E. , Cardamone Nicholas C. , Loscalzo Emily , French Rachel , Lovelace Collin , Mowenn Winna Koe , Tarhini Ali , Lalley-Chareczko Linden , Brady Kathleen A. , Mandell David S.
Published: March 2023

Background

Vending machines for harm reduction (VMHR) are an innovative approach to deliver life-saving materials, information, and treatment for hard-to-reach populations, particularly for persons who inject drugs. The current study explores stakeholders’ perspectives on the feasibility and acceptability of VMHR in Philadelphia.

Methods

From October 2021 to February 2022, we conducted 31 semi-structured interviews with potential end users, staff, and leadership at a local federally qualified health center, and community members. Trained coders extracted themes from interview transcripts across four key domains: materials and logistics, location, access, and community introduction.

Results

Interviewees from all stakeholder groups endorsed using VMHR to provide supplies for wound care, fentanyl test strips, naloxone, and materials to connect individuals to treatment and other services. Dispensing syringes and medications for opioid use disorder were commonly endorsed by health center staff but were more controversial among potential end users. Even within stakeholder groups, views varied with respect to where to locate the machines, but most agreed that the machine should be placed in the highest drug use areas. Across stakeholder groups, interviewees suggested several strategies to introduce and gain community acceptance of VMHR, including community education, one-on-one conversations with community members, and coupling the machine with safe disposal of syringes and information to link individuals to treatment.

Conclusions

Stakeholders were generally receptive to VMHR. The current study findings are consistent with qualitative analyses from outside of the USA and contribute new ideas regarding the anticipated community response and best methods for introducing these machines to a community. With thoughtful planning and design, VMHR could be a feasible and acceptable modality to reduce death and disease transmission associated with the opioid and HIV epidemics in cities like Philadelphia.
Exogenous monocyte myeloid-derived suppressor cells ameliorate immune imbalance, neuroinflammation and cognitive impairment in 5xFAD mice infected with Porphyromonas gingivalis
Authors: Cheng Xiao , Chi Li , Lin Tianqiong , Liang Fengyin , Pei Zhong , Sun Jianbo , Teng Wei
Published: March 2023

Background

Periodontitis is closely associated with the pathogenesis of Alzheimer’s disease (AD). Porphyromonas gingivalis (Pg), the keystone periodontal pathogen, has been reported in our recent study to cause immune-overreaction and induce cognitive impairment. Monocytic myeloid-derived suppressor cells (mMDSCs) possess potent immunosuppressive function. It is unclear whether mMDSCs-mediated immune homeostasis is impaired in AD patients with periodontitis, and whether exogenous mMDSCs could ameliorate immune-overreaction and cognitive impairment induced by Pg.

Methods

To explore the influence of Pg on cognitive function, neuropathology and immune balance in vivo, 5xFAD mice were treated with live Pg by oral gavage, three times a week for 1 month. The cells of peripheral blood, spleen and bone marrow from 5xFAD mice were treated with Pg to detect the proportional and functional alterations of mMDSCs in vitro. Next, exogenous mMDSCs were sorted from wild-type healthy mice and intravenously injected into 5xFAD mice that were infected with Pg. We used behavioral tests, flow cytometry and immunofluorescent staining to evaluate whether exogenous mMDSCs could ameliorate the cognitive function, immune homeostasis and reduce neuropathology exacerbated by Pg infection.

Results

Pg exacerbated cognitive impairment in 5xFAD mice, with the deposition of amyloid plaque and increased number of microglia in the hippocampus and cortex region. The proportion of mMDSCs decreased in Pg-treated mice. In addition, Pg reduced the proportion and the immunosuppressive function of mMDSCs in vitro. Supplement of exogenous mMDSCs improved the cognitive function, and enhanced the proportions of mMDSCs and IL-10+ T cells of 5xFAD mice infected with Pg. At the same time, supplement of exogenous mMDSCs increased the immunosuppressive function of endogenous mMDSCs while decreased the proportions of IL-6+ T cells and IFN-γ+ CD4+ T cells. In addition, the deposition of amyloid plaque decreased while the number of neurons increased in the hippocampus and cortex region after the supplement of exogenous mMDSCs. Furthermore, the number of microglia increased with an increase in the proportion of M2 phenotype.

Conclusions

Pg can reduce the proportion of mMDSCs, induce immune-overreaction, and exacerbate the neuroinflammation and cognitive impairment in 5xFAD mice. Supplement of exogenous mMDSCs can reduce the neuroinflammation, immune imbalance and cognitive impairment in 5xFAD mice infected with Pg. These findings indicate the mechanism of AD pathogenesis and Pg-mediated promotion of AD, and provide a potential therapeutic strategy for AD patients.
A comprehensive immunohistochemical analysis of 26 markers in 250 cases of serous ovarian tumors
Authors: Němejcová Kristýna , Šafanda Adam , Bártů Michaela Kendall , Michálková Romana , Drozenová Jana , Fabian Pavel , Hausnerová Jitka , Laco Jan , Matěj Radoslav , Méhes Gábor , Škapa Petr , Stružinská Ivana , Dundr Pavel
Published: March 2023

Background

We examined a large cohort of serous tubo-ovarian tumors with 26 immunohistochemical markers, with the aim to assess their value for differential diagnosis and prognosis.

Methods

Immunohistochemical analyses with 26 immunomarkers were performed on 250 primary tubo-ovarian tumors including 114 high grade serous carcinomas (HGSC), 97 low grade serous carcinomas (LGSC), and 39 serous borderline tumors (micropapillary variant, mSBT). The associations of overall positivity with clinicopathological characteristics were evaluated using the chi-squared test or Fisher’s Exact test.

Results

We found significantly different expression of p53, p16, ER, PR, PTEN, PAX2, Mammaglobin, RB1, Cyclin E1, stathmin, LMP2, L1CAM, CD44, and Ki67 in HGSCs compared to LGSCs. No significant differences were found between LGSC and mSBT. None of the other included markers (PAX8, ARID1A, HNF1B, Napsin A, CDX2, SATB2, MUC4, BRG1, AMACR, TTF1, BCOR, NTRK) showed any differences between the investigated serous tumors. Regarding the prognosis, only PR and stathmin showed a statistically significant prognostic meaning in LGSCs, with better overall survival (OS) and recurrence-free survival (RFS) in cases positive for PR, and worse outcome (RFS) for stathmin. None of the study markers showed prognostic significance in HGSCs.

Conclusion

We provided an extensive immunohistochemical analysis of serous ovarian/tubo-ovarian tumors. Although we found some differences in the expression of some markers in HGSCs compared to LGSCs, only p53, p16, and Ki67 seem to be useful in real diagnostic practice. We also suggested the best discriminative cut-off for Ki67 (10% of positive tumor cells) for distinguishing HGSC from LGSC. We found prognostic significance of PR and stathmin in LGSCs. Moreover, the high expression of stathmin could also be of predictive value in ovarian carcinomas as target-specific anti-stathmin effectors are potential therapeutic targets.
A new biotechnology for in-planta gene editing and its application in promoting flavonoid biosynthesis in bamboo leaves
Authors: Sun Huayu , Wang Sining , Zhu Chenglei , Yang Kebin , Liu Yan , Gao Zhimin
Published: March 2023

Background

Bamboo is a perennial and renewable biomass forest resource and its leaf flavonoid is an antioxidant for biological and pharmacological research. The established genetic transformation and gene editing systems in bamboo are significantly limited by the dependence on bamboo regeneration capability. The way to improve the flavonoid content in bamboo leaves through biotechnology is still not feasible.

Results

Here, we developed an in-planta, Agrobacterium-mediated gene expression method for exogenous genes via wounding and vacuum in bamboo. We demonstrated that the RUBY served as a reporter efficiently expressed in bamboo leaves and shoots, albeit unable to integrate into the chromosome. We have also developed a gene editing system by creating an in situ mutant of the bamboo violaxanthin de-epoxidase (PeVDE) gene in bamboo leaves, with lower NPQ values under the fluorometer, which can serve as a native reporter for gene editing. Furthermore, the bamboo leaves with increased flavonoid content were achieved by knocking out the cinnamoyl-CoA reductase genes.

Conclusions

Our method can be applied for the functional characterization of novel genes in a short time and is helpful for bamboo leaf flavonoid biotechnology breeding in the future.
Nesfatin-1 suppresses autophagy of chondrocytes in osteoarthritis via remodeling of cytoskeleton and inhibiting RhoA/ROCK signal pathway
Authors: Jiang Lifeng , Moqbel Safwat Adel Abdo , Zhu Junxiong , Fu Qiangchang , Lai Jiabin , Lin Changjian , Wu Lidong
Published: March 2023

Autophagy and cytoskeleton integrity of chondrocytes are a considered as major factors in the progression of osteoarthritis (OA) involving excessive chondrocyte apoptosis and senescence. Nesfatin-1, an adipokine, has been reported to be closely related to cell autophagy and cytoskeleton malfunction. Our previous study found that nesfatin-1 was highly correlated with OA progress in OA patient, and the expression of nesfatin-1 rises in knee articular tissue, serum and chondrocytes. In current study, we aimed to explore the therapeutic effect of nesfatin-1 on OA and its molecular mechanism related to chondrocyte autophagy and cytoskeleton malfunction. We firstly demonstrated that nesfatin-1 effectively suppressed excessive autophagy of OA chondrocytes at both gene and protein levels. Meanwhile, we also found that nesfatin-1 significantly improved cytoskeleton integrity by showing higher F-actin/G-actin ratio, as well as more organized actin fiber structure. Mechanistically, utility of RhoA activator and inhibitor revealed that regulation of autophagy and cytoskeleton integrity via nesfatin-1 was realized via RhoA/ROCK pathway. We also confirmed that nesfatin-1 significantly ameliorated IL-1β induced cartilage degeneration via destabilization of the medial meniscus (DMM) model. Overall, our study indicates that nesfatin-1 might be a promising therapeutic molecule for OA intervention.
Analysis of the cost-efficiency of the vascular impulse technology (VIT) in the perioperative management of complex ankle fractures: results of a prospective randomised controlled trial
Authors: El Barbari Jan S. , Schnetzke Marc , Swartman Benedict , Grützner Paul A. , Franke Jochen
Published: March 2023

Introduction

Posttraumatic swelling causes a delay in surgery, a prolonged hospital stay and a higher risk of complications. Thus, soft tissue conditioning following complex ankle fractures is of central importance in their perioperative management. Since the clinical benefit of VIT usage on the clinical course has been shown, it should now be investigated whether it is also cost-efficient in doing so.

Materials and methods

Included are published clinical results of the prospective, randomised, controlled, monocentric VIT study that have proven the therapeutic benefit in complex ankle fractures. Participants were allocated in a 1:1 ratio into the intervention group (VIT) and the control group (elevation). In this study, the required economic parameters of these clinical cases were collected on the data of the financial accounting and an estimation of annual cases had been performed to extrapolate the cost-efficiency of this therapy. The primary endpoint was the mean savings (in €).

Results

Thirty-nine cases were studied in the period from 2016 to 2018. There was no difference in the generated revenue. However, due to lower incurred costs in the intervention group, there were potential savings of about €2000 (pITT = 0.073) to 3000 (pAT = 0.008) per patient compared to the control group with therapy costs decreasing as the number of patients treated increases from €1400 in one case to below €200 per patient in 10 cases. There were 20% more revision surgeries in the control group or 50 min more OR time, respectively, and an increased attendance by staff and medical personnel of more than 7 h.

Conclusions

VIT therapy has been shown to be a beneficial therapeutic modality, but it is so not only in regard to soft-tissue conditioning but also cost efficiency.
The promotive role of USP1 inhibition in coordinating osteogenic differentiation and fracture healing during nonunion
Authors: Huang Jun , Zhou Hongxiang , He Liang , Zhong Lin , Zhou Ding , Yin Zongsheng
Published: March 2023

Background

Nonunion is a failure of fracture healing and a major complication after fractures. Ubiquitin-specific protease 1 (USP1) is a deubiquitinase that involved in cell differentiation and cell response to DNA damage. Herein we investigated the expression, function and mechanism of USP1 in nonunion.

Methods and results

Clinical samples were used to detect the USP1 expression in nonunion. ML323 was selected to inhibit USP1 expression throughout the study. Rat models and mouse embryonic osteoblasts cells (MC3T3-E1) were used to investigate the effects of USP1 inhibition on fracture healing and osteogenesis in vivo and in vitro, respectively. Histological changes were examined by micro-computerized tomography (Micro-CT), hematoxylin & eosin (H&E) staining and Masson staining. Alkaline phosphatase (ALP) activity detection and alizarin red staining were used for osteogenic differentiation observation. The expression of related factors was detected by quantitative real-time PCR, western blot or immunohistochemistry (IHC). It was shown that USP1 was highly expressed in nonunion patients and nonunion rats. USP1 inhibition by ML323 promoted fracture healing in nonunion rats and facilitated the expression of osteogenesis-related factors and the signaling of PI3K/Akt pathway. In addition, USP1 inhibition accelerated osteogenic differentiation and promoting PI3K/Akt signaling in MC3T3-E1 cells.

Conclusions

USP1 inhibition plays a promotive role in coordinating osteogenic differentiation and fracture healing during nonunion. PI3K/Akt may be the downstream pathway of USP1.
Evidence-based informed consent form for total knee arthroplasty
Authors: Pai Satvik N. , Jeyaraman Madhan , Maffulli Nicola , Jeyaraman Naveen , Migliorini Filippo , Gupta Ashim
Published: March 2023

Introduction

Informed consent documentation is often the first area of interest for lawyers and insurers when a medico-legal malpractice suit is concerned. However, there is a lack of uniformity and standard procedure about obtaining informed consent for total knee arthroplasty (TKA). We developed a solution for this need for a pre-designed, evidence-based informed consent form for patients undergoing TKA.

Materials and methods

We extensively reviewed the literature on the medico-legal aspects of TKA, medico-legal aspects of informed consent, and medico-legal aspects of informed consent in TKA. We then conducted semi-structured interviews with orthopaedic surgeons and patients who had undergone TKA in the previous year. Based on all of the above, we developed an evidence-based informed consent form. The form was then reviewed by a legal expert, and the final version was used for 1 year in actual TKA patients operated at our institution.

Results

Legally sound, evidence-based Informed Consent Form for Total Knee Arthroplasty.

Conclusion

The use of legally sound, evidence-based informed consent for total knee arthroplasty would be beneficial to orthopaedic surgeons and patients alike. It would uphold the rights of the patient, promote open discussion and transparency. In the event of a lawsuit, it would be a vital document in the defence of the surgeon and withstand the scrutiny of lawyers and the judiciary.
Radiological features accompanying peroneus brevis split rupture revealed on magnetic resonance imaging – a cohort study
Authors: Huuskonen Michael , Borkmann Simon , Bengtsson Alexander , Sobecki Piotr , Józwiak Rafał , Solidakis Nektarios , Szaro Paweł
Published: March 2023

Background

Peroneal split tears are an underrated cause of ankle pain. While magnetic resonance imaging (MRI) is useful for diagnosis, split tears are challenging to identify. The aim of the study was to investigate the association of peroneus brevis split rupture with abnormalities of the superior peroneal retinaculum (SPR), anterior talofibular ligament (ATFL), calcaneofibular ligament (CFL), joint effusion, morphology of the malleolar groove, presence of the bone marrow oedema and prominent peroneal tuberculum.

Methods

Ankle MRI cases were assessed by independent observers retrospectively in two groups: one with peroneus brevis split tears (n = 80) and one without (control group, n = 115). Two observers evaluated the soft tissue lesions, and three graded the bone lesions. Fisher's exact test and Pearson correlation were used for analysis. The Bonferroni‐Holm method (B‐H) was used to adjust for multiple comparisons.

Results

Only bone marrow edema in the posterior part of the lateral malleolus was significantly (p < 0.05) more common in the split tear group after applying B‐H. SPR total rupture was seen only in the experimental group. No differences in incidence of ATFL and CFL lesions or other SPR lesions were noticed (p < 0.05).

Conclusion

Bone marrow edema in the posterior part of the lateral malleolus is associated with peroneus split tears on MRI.
Improving vasopressor use in cardiac arrest
Authors: Perkins Gavin D. , Couper Keith
Published: March 2023

The Chain of Survival highlights the effectiveness of early recognition of cardiac arrest and call for help, early cardiopulmonary resuscitation and early defibrillation. Most patients, however, remain in cardiac arrest despite these interventions. Drug treatments, particularly the use of vasopressors, have been included in resuscitation algorithms since their inception. This narrative review describes the current evidence base for vasopressors and reports that adrenaline (1 mg) is highly effective at achieving return of spontaneous circulation (number needed to treat 4) but is less effective on long-term outcomes (survival to 30 days, number needed to treat 111) with uncertain effects on survival with a favourable neurological outcome. Randomised trials evaluating vasopressin, either as an alternative to or in addition to adrenaline, and high-dose adrenaline have failed to find evidence of improved long-term outcomes. There is a need for future trials to evaluate the interaction between steroids and vasopressin. Evidence for other vasopressors (e.g. noradrenaline, phenylephedrine) is insufficient to support or refute their use. The use of intravenous calcium chloride as a routine intervention in out of hospital cardiac arrest is not associated with benefit and may cause harm. The optimal route for vascular access between peripheral intravenous versus intraosseous routes is currently the subject of two large randomised trials. Intracardiac, endobronchial, and intramuscular routes are not recommended. Central venous administration should be limited to patients where an existing central venous catheter is in situ and patent.
Prevalence of diabetic retinopathy in Brazil: a systematic review with meta-analysis
Authors: Chagas Thiago Alves , dos Reis Mateus Augusto , Leivas Gabriel , Santos Lucas Porto , Gossenheimer Agnes Nogueira , Melo Gustavo Barreto , Malerbi Fernando Korn , Schaan Beatriz D.
Published: March 2023

Aims

To evaluate the prevalence of diabetic retinopathy (DR) in Brazilian adults with diabetes mellitus via a systematic review with meta-analysis.

Methods

A systematic review using PubMed, EMBASE, and Lilacs was conducted, searching for studies published up to February 2022. Random effect meta-analysis was performed to estimate the DR prevalence.

Results

We included 72 studies (n = 29,527 individuals). Among individuals with diabetes in Brazil, DR prevalence was 36.28% (95% CI 32.66–39.97, I2 98%). Diabetic retinopathy prevalence was highest in patients with longer duration of diabetes and in patients from Southern Brazil.

Conclusion

This review shows a similar prevalence of DR as compared to other low- and middle-income countries. However, the high heterogeneity observed—expected in systematic reviews of prevalence—raises concerns about the interpretation of these results, suggesting the need for multicenter studies with representative samples and standardized methodology.
Disruption of early visual processing in amyloid-positive healthy individuals and mild cognitive impairment
Authors: Javitt Daniel C. , Martinez Antigona , Sehatpour Pejman , Beloborodova Anna , Habeck Christian , Gazes Yunglin , Bermudez Dalton , Razlighi Qolamreza R. , Devanand D. P. , Stern Yaakov
Published: March 2023

Background

Amyloid deposition is a primary predictor of Alzheimer’s disease (AD) and related neurodegenerative disorders. Retinal changes involving the structure and function of the ganglion cell layer are increasingly documented in both established and prodromal AD. Visual event-related potentials (vERP) are sensitive to dysfunction in the magno- and parvocellular visual systems, which originate within the retinal ganglion cell layer. The present study evaluates vERP as a function of amyloid deposition in aging, and in mild cognitive impairment (MCI).

Methods

vERP to stimulus-onset, motion-onset, and alpha-frequency steady-state (ssVEP) stimuli were obtained from 16 amyloid-positive and 41 amyloid-negative healthy elders and 15 MCI individuals and analyzed using time–frequency approaches. Social cognition was assessed in a subset of individuals using The Awareness of Social Inference Test (TASIT).

Results

Neurocognitively intact but amyloid-positive participants and MCI individuals showed significant deficits in stimulus-onset (theta) and motion-onset (delta) vERP generation relative to amyloid-negative participants (all p < .01). Across healthy elders, a composite index of these measures correlated highly (r =  − .52, p < .001) with amyloid standardized uptake value ratios (SUVR) and TASIT performance. A composite index composed of vERP measures significant differentiated amyloid-positive and amyloid-negative groups with an overall classification accuracy of > 70%.

Discussion

vERP may assist in the early detection of amyloid deposition among older individuals without observable neurocognitive impairments and in linking previously documented retinal deficits in both prodromal AD and MCI to behavioral impairments in social cognition.
Using participatory epidemiology to investigate women’s knowledge on the seasonality and causes of acute malnutrition in Karamoja, Uganda
Authors: Catley Andy , Arasio Raphael Lotira , Hopkins Charles
Published: March 2023

The Karamoja region of northeast Uganda had been characterized by high levels of acute malnutrition (AM) for decades, despite substantial aid investment in nutrition programmes. Participatory epidemiology (PE) was used to understand the seasonality of child AM from the perspective of women agro-pastoralists and understand their knowledge and prioritization of the causes of child AM. Women provided highly plausible descriptions and analysis of monthly variations in the occurrence of AM, livelihood factors related to the temporal variation in AM occurrence, the root causes of AM and relationships between these causes. Overall, AM was strongly attributed to declining livestock ownership and access to cow milk and normalized gender discrimination. Monthly calendars revealed important monthly patterns in AM, births and women’s workload that had not been previously reported. There was significant agreement (p < 0.01) between independent women’s groups (n = 16) for the monthly calendars and causal diagrams, indicating strong reproducibility of the methods. Triangulation indicated good validity of the monthly calendar method. The PE approach demonstrated that agro-pastoralist women with limited formal education could describe and analyse the seasonality of AM and related factors and identify and prioritize the causes of AM. Indigenous knowledge should be valued and respected, and nutrition programmes should shift the emphasis towards far more participatory and community-based approaches. The timing of conventional nutrition surveys in agro-pastoral settings should be based on an understanding of the seasonality of livelihoods.
Activation of the Hedgehog signaling pathway leads to fibrosis in aortic valves
Authors: Gu Dongsheng , Soepriatna Arvin H. , Zhang Wenjun , Li Jun , Zhao Jenny , Zhang Xiaoli , Shu Xianhong , Wang Yongshi , Landis Benjamin J. , Goergen Craig J. , Xie Jingwu
Published: March 2023

Background

Fibrosis is a pathological wound healing process characterized by excessive extracellular matrix deposition, which interferes with normal organ function and contributes to ~ 45% of human mortality. Fibrosis develops in response to chronic injury in nearly all organs, but the a cascade of events leading to fibrosis remains unclear. While hedgehog (Hh) signaling activation has been associated with fibrosis in the lung, kidney, and skin, it is unknown whether hedgehog signaling activation is the cause or the consequence of fibrosis. We hypothesize that activation of hedgehog signaling is sufficient to drive fibrosis in mouse models.

Results

In this study, we provide direct evidence to show that activation of Hh signaling via expression of activated smoothened, SmoM2, is sufficient to induce fibrosis in the vasculature and aortic valves. We showed that activated SmoM2 -induced fibrosis is associated with abnormal function of aortic valves and heart. The relevance of this mouse model to human health is reflected in our findings that elevated GLI expression is detected in 6 out of 11 aortic valves from patients with fibrotic aortic valves.

Conclusions

Our data show that activating hedgehog signaling is sufficient to drive fibrosis in mice, and this mouse model is relevant to human aortic valve stenosis.
Different interventions for the treatment of patent ductus arteriosus in children: a protocol for a network meta-analysis
Authors: Zhang Xin , Hou Xiao-Dong , Wang Wen-Xin , Yi Kang , Wang Xin-Kuan , Ding Fan , Li Xin-Xin , You Tao
Published: March 2023

Introduction

Patent ductus arteriosus (PDA) is one of the most common congenital heart diseases. Once the PDA is diagnosed, it needs to be dealt with in time. At present, main methods include pharmacological treatment, surgical closure, and interventional closure for treatment of PDA. However, the effect of different interventions in PDA management is still controversial. Thus, our study aims to assess the effectiveness of different interventions together and estimate the sequence of these therapies for PDA children. Meanwhile, it is necessary to conduct a Bayesian network meta-analysis to compare the safety of different interventions comprehensively.

Methods and analysis

To the best of our knowledge, this is the first Bayesian network meta-analysis comparing the efficacy and safety of different interventions for the treatment of PDA. PubMed, Embase, Cochrane Library, Web of Science, gray literature, and trial registry databases were searched from inception to December 2022. We will extract and report data according to methodological guidelines for Bayesian network meta-analysis by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P). Primary PDA closure, overall PDA closure, technical success, surgical success rate, mortality during hospital stay, operation time, intensive care unit stay, intraoperative radiation dose, radiation exposure time, total postoperative complication rate, and postoperative major complication rate will be defined as the outcomes. The quality of all random studies will be assessed using ROB, and quality of evidence for all outcomes will be judged by using the Grading of Recommendations Assessment, Development and Evaluation (GRADE).

Ethics and dissemination

The results will be disseminated through peer-reviewed publication. Since no private and confidential patient data will be contained in the reporting, there are no ethical considerations associated with this protocol.

Systematic review registration

INPLASY2020110067.
Beyond guideline knowledge: a theory-based qualitative study of low-value preoperative testing
Authors: Jasaui Yamile , Mortazhejri Sameh , Dowling Shawn , Duquette D’Arcy , L’Heureux Geralyn , Linklater Stefanie , Mrklas Kelly J. , Wilkinson Gloria , Beesoon Sanjay , Patey Andrea M. , Ruzycki Shannon M. , Grimshaw Jeremy M. ,   on behalf of the De-Implementing Wisely Research Group
Published: March 2023

Background

Choosing Wisely Canada and most major anesthesia and preoperative guidelines recommend against obtaining preoperative tests before low-risk procedures. However, these recommendations alone have not reduced low-value test ordering. In this study, the theoretical domains framework (TDF) was used to understand the drivers of preoperative electrocardiogram (ECG) and chest X-ray (CXR) ordering for patients undergoing low-risk surgery (‘low-value preoperative testing’) among anesthesiologists, internal medicine specialists, nurses, and surgeons.

Methods

Using snowball sampling, preoperative clinicians working in a single health system in Canada were recruited for semi-structured interviews about low-value preoperative testing. The interview guide was developed using the TDF to identify the factors that influence preoperative ECG and CXR ordering. Interview content was deductively coded using TDF domains and specific beliefs were identified by grouping similar utterances. Domain relevance was established based on belief statement frequency, presence of conflicting beliefs, and perceived influence over preoperative test ordering practices.

Results

Sixteen clinicians (7 anesthesiologists, 4 internists, 1 nurse, and 4 surgeons) participated. Eight of the 12 TDF domains were identified as the drivers of preoperative test ordering. While most participants agreed that the guidelines were helpful, they also expressed distrust in the evidence behind them (knowledge). Both a lack of clarity about the responsibilities of the specialties involved in the preoperative process and the ease by which any clinician could order, but not cancel tests, were drivers of low-value preoperative test ordering (social/professional role and identity, social influences, belief about capabilities). Additionally, low-value tests could also be ordered by nurses or the surgeon and may be completed before the anesthesia or internal medicine preoperative assessment appointment (environmental context and resources, beliefs about capabilities). Finally, while participants agreed that they did not intend to routinely order low-value tests and understood that these would not benefit patient outcomes, they also reported ordering tests to prevent surgery cancellations and problems during surgery (motivation and goals, beliefs about consequences, social influences).

Conclusions

We identified key factors that anesthesiologists, internists, nurses, and surgeons believe influence preoperative test ordering for patients undergoing low-risk surgeries. These beliefs highlight the need to shift away from knowledge-based interventions and focus instead on understanding local drivers of behaviour and target change at the individual, team, and institutional levels.
The molecular epidemiology, genotyping, and clinical manifestation of prevalent adenovirus infection during the epidemic keratoconjunctivitis, South of Iran
Authors: Afrasiabi Vahidreza , Ghojoghi Rozita , Hosseini Seyed Younes , Sarvari Jamal , Nekooei Fatemeh , Joharinia Negar , Hadian Sahar , Gholami Mohammad , Nejabat Mahmood
Published: March 2023

Purpose

Adenoviral-mediated keratoconjunctivitis is among the emergency diseases of ophthalmology with long-term sequels. The role of adenovirus infection, ocular-related genotypes, and association with ocular symptoms need to be investigated for epidemiological as well as clinical purposes.

Methods

The affected patients from two close keratoconjunctivitis epidemics were included in the study. The swab samples were taken from patients; the total DNA was extracted and then used as a template for in-house Real-time PCR. Besides, partial Hexon genes of 11 adenovirus positive samples were amplified and submitted to sanger sequencing. Moreover, they were finally evaluated by phylogenetic analysis.

Results

Of 153 patients, 92 (60.1%) were males and 47 cases (30.7%) had a history of eye infection in the family or colleagues. Real-time PCR tests of 126 samples (82.4%) were positive for adenovirus, and all eleven cases that underwent sequencing analysis were determined to be group 8 (HAdV-D8). Adenovirus infection has a significant relationship with infection among family or colleagues (p = 0.048), membrane formation (p = 0.047), conjunctival bleeding (p = 0.046), tearing, and pain(p < 0.05).

Conclusions

The results indicated that Adenovirus is the major cause of keratoconjunctivitis, and HAdV-D8 was the most common genotype in the area. There were some clinical manifestations associated with Adenovirus infection of the conjunctiva.
The effect of selenium therapy in critically ill patients: an umbrella review of systematic reviews and meta-analysis of randomized controlled trials
Authors: Jaff Salman , Zeraattalab-Motlagh Sheida , Amiri Khosroshahi Reza , Gubari Mohammed , Mohammadi Hamed , Djafarian Kurosh
Published: March 2023

Background

Selenium is an essential nutrient with antioxidant, anti-inflammatory, and immuno-regulatory properties. Studies have displayed that in critically ill patients, selenium supplementation may be a potentially promising adjunctive therapy.

Objective

We aimed to present an overview of the effects of selenium supplementation in adult critically ill patients based on published systematic reviews and meta-analyses (SRMAs) of randomized controlled trials (RCTs).

Methods

A literature search in three electronic databases, PubMed, Scopus, and Web of Science, was performed to find eligible SRMAs until July 2022. For each outcome, the risk ratios (RRs) or mean differences (MDs) and 95% confidence intervals (CIs) were recalculated using either random or fixed effect models. The methodological quality and quality of evidence of the SRMAs were assessed by applying “A Measurement Tool to Assess Systematic Reviews” (AMSTAR2) and Grading of Recommendations Assessment, Development, and Evaluation(GRADE) tools, respectively.

Results

We included 17 meta-analyses containing 24 RCTs based on inclusion criteria. Selenium supplementation can reduce the incidence of mortality (RR: 0.83, 95% CI 0.71, 0.98, P = 0.024) and incidence of acute renal failure (RR: 0.67, 95% CI 0.46, 0.98, P: 0.038) significantly; however, the certainty of evidence was low. Moreover, with moderate to very low certainty of evidence, no significant effects were found for risk of infection (RR: 0.92, 95% CI 0.80, 1.05, P: 0.207), pneumonia (RR: 1.11, 95% CI 0.72, 1.72, P: 0.675), as well as the length of ICU (MD: 0.15, 95% CI − 1.75, 2.05, P: 0.876) and hospital stay (MD: − 0.51, 95% CI − 3.74, 2.72, P: 0.757) and days on ventilation (MD: − 0.98, 95% CI − 2.93, 0.98, P: 0.329).

Conclusions

With low quality of evidence, the use of selenium supplementation could improve the risk of mortality and acute renal failure, but not other outcomes in critically ill patients.
Machine learning determination of applied behavioral analysis treatment plan type
Authors: Maharjan Jenish , Garikipati Anurag , Dinenno Frank A. , Ciobanu Madalina , Barnes Gina , Browning Ella , DeCurzio Jenna , Mao Qingqing , Das Ritankar
Published: March 2023

Background

Applied behavioral analysis (ABA) is regarded as the gold standard treatment for autism spectrum disorder (ASD) and has the potentialto improve outcomes for patients with ASD. It can be delivered at different intensities, which are classified as comprehensive or focused treatment approaches. Comprehensive ABA targets multiple developmental domains and involves 20–40 h/week of treatment. Focused ABA targets individual behaviors and typically involves 10–20 h/week of treatment. Determining the appropriate treatment intensity involves patient assessment by trained therapists, however, the final determination is highly subjective and lacks a standardized approach. In our study, we examined the ability of a machine learning (ML) prediction model to classify which treatment intensity would be most suited individually for patients with ASD who are undergoing ABA treatment.

Methods

Retrospective data from 359 patients diagnosed with ASD were analyzed and included in the training and testing of an ML model for predicting comprehensive or focused treatment for individuals undergoing ABA treatment. Data inputs included demographics, schooling, behavior, skills, and patient goals. A gradient-boosted tree ensemble method, XGBoost, was used to develop the prediction model, which was then compared against a standard of care comparator encompassing features specified by the Behavior Analyst Certification Board treatment guidelines. Prediction model performance was assessed via area under the receiver-operating characteristic curve (AUROC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).

Results

The prediction model achieved excellent performance for classifying patients in the comprehensive versus focused treatment groups (AUROC: 0.895; 95% CI 0.811–0.962) and outperformed the standard of care comparator (AUROC 0.767; 95% CI 0.629–0.891). The prediction model also achieved sensitivity of 0.789, specificity of 0.808, PPV of 0.6, and NPV of 0.913. Out of 71 patients whose data were employed to test the prediction model, only 14 misclassifications occurred. A majority of misclassifications (n = 10) indicated comprehensive ABA treatment for patients that had focused ABA treatment as the ground truth, therefore still providing a therapeutic benefit. The three most important features contributing to the model’s predictions were bathing ability, age, and hours per week of past ABA treatment.

Conclusion

This research demonstrates that the ML prediction model performs well to classify appropriate ABA treatment plan intensity using readily available patient data. This may aid with standardizing the process for determining appropriate ABA treatments, which can facilitate initiation of the most appropriate treatment intensity for patients with ASD and improve resource allocation.
Analytical bifurcation behaviors of a host–parasitoid model with Holling type III functional response
Authors: Yousef Ahmed M. , Rida Saad Z. , Arafat Soheir
Published: March 2023

This topic presents a study on a host–parasitoid model with a Holling type III functional response. In population dynamics, when host density rises, the parasitoid response initially accelerates due to the parasitoid’s improved searching efficiency. However, above a certain density threshold, the parasitoid response will reach a saturation level due to the influence of reducing the handling time. Thus, we incorporated a Holling type III functional response into the model to characterize such a phenomenon. The dynamics of the current model are discussed in this paper. We first obtained the existence and local stability conditions of the positive fixed point of the model. Furthermore, we investigated the bifurcation behaviors at the positive fixed point. More specifically, we used bifurcation theory and the center manifold theorem to prove that the model possess both period doubling and Neimark–Sacker bifurcations. Then, the chaotic behavior of the model, in the sense of Marotto, is proven. Furthermore, we apply a state-delayed feedback control strategy to control the complex dynamics of the present model. Finally, numerical examples are provided to support our analytic results.
Quantitative Biology at Community Colleges, a Network of Biology and Mathematics Faculty Focused on Improving Numerical and Quantitative Skills of Students
Authors: Esquibel Joseph , Rook Deborah L. , LoRe Sondra M. , Starnes John H. , Miller Jillian M. , Buntz Jennifer G. , Hugo Alys , Nieuwsma Christianne B. , Seitz Heather , Bissell Ahrash , Gross Louis , Kiser Stacey , Lenhart Suzanne , Mills Michael A. , Neuhauser Claudia , Corriette Irene , Prescott Sarah , Jenkins Kristin P. , Karpakakunjaram Vedham
Published: March 2023

Quantitative Biology at Community Colleges (QB@CC) is an NSF-funded, RCN-UBE grant that builds collaborative teams of biology, mathematics, and statistics faculty from community colleges across the United States to generate ready-to-implement, open-access modules that integrate math and biology content. QB@CC provides professional development opportunities for faculty to strategize teaching quantitative skills as part of biology curriculum.
Current Insights
Authors: Eddy Sarah L.
Published: March 2023

This installment of Current Insights reviews three articles that 1) characterize how instructor beliefs about intelligence are communicated to students, 2) explore the connection between instructor research and teaching identities, and 3) investigate how to broaden the definitions of student success used in research.
Ethnic differences in response to atypical antipsychotics in patients with schizophrenia: individual patient data meta-analysis of randomised placebo-controlled registration trials submitted to the Dutch Medicines Evaluation Board
Authors: Storosum Bram W. C. , Steinz Cedrine , Cohen Sem E. , Mattila Taina , Brink Wim van den , Roes Kit , de Haan Lieuwe , Denys Damiaan A. J. P. , Zantvoord Jasper B.
Published: March 2023

Background

Little is known about the effect of ethnicity on the response to antipsychotic medication in patients with schizophrenia.

Aims

To determine whether ethnicity moderates the response to antipsychotic medication in patients with schizophrenia, and whether this moderation is independent of confounders.

Method

We analysed 18 short-term, placebo-controlled registration trials of atypical antipsychotic medications in patients with schizophrenia (N = 3880). A two-step, random-effects, individual patient data meta-analysis was applied to establish the moderating effect of ethnicity (White versus Black) on symptom improvement according to the Brief Psychiatric Rating Scale (BPRS) and on response, defined as >30% BPRS reduction. These analyses were corrected for baseline severity, baseline negative symptoms, age and gender. A conventional meta-analysis was performed to determine the effect size of antipsychotic treatment for each ethnic group separately.

Results

In the complete data-set, 61% of patients were White, 25.6% of patients were Black and 13.4% of patients were of other ethnicities. Ethnicity did not moderate the efficacy of antipsychotic treatment: pooled β-coefficient for the interaction between treatment and ethnic group was −0.582 (95% CI −2.567 to 1.412) for mean BPRS change, with an odds ratio of 0.875 (95% CI 0.510–1.499) for response. These results were not modified by confounders.

Conclusions

Atypical antipsychotic medication is equally effective in both Black and White patients with schizophrenia. In registration trials, White and Black patients were overrepresented relative to other ethnic groups, limiting the generalisability of our findings.
Neoadjuvant Immune Checkpoint Inhibitor Therapy for Patients With Microsatellite Instability-High Colorectal Cancer: Shedding Light on the Future
Authors: Sahin Ibrahim Halil , Zhang Janie , Saridogan Turcin , Gorantla Vikram , Rhree John , Malhotra Monica , Thomas Roby , Hsu Dennis , Saeed Anwaar
Published: March 2023

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment paradigm of mismatch repair–deficient/microsatellite instability-high (MMMR-D/MSI-H) colorectal cancer (CRC). Unique molecular features of MMR-D/MSI-H CRC with frameshift alterations, which result in mutation-associated neoantigen (MANA) generation, create an ideal molecular framework for MANA-driven T-cell priming and antitumor immunity. These biologic characteristics of MMR-D/MSI-H CRC resulted in rapid drug development with ICIs for patients with MMR-D/MSI-H CRC. Observed deep and durable responses with the use of ICIs in advanced-stage disease have stimulated the development of clinical trials with ICIs for patients with early-stage MMR-D/MSI-H CRC. Most recently, neoadjuvant dostarlimab monotherapy for nonoperative management of MMR-D/MSI-H rectal cancer and neoadjuvant NICHE trial with nivolumab and ipilimumab for MMR-D/MSI-H colon cancer resulted in groundbreaking results. Although nonoperative management of patients with MMR-D/MSI-H rectal cancer with ICIs will potentially define our current therapeutic approach, therapeutic goals of neoadjuvant ICI therapy for patients with MMR-D/MSI-H colon cancer may differ given that nonoperative management has not been well established for colon cancer. Herein, we overview recent advancements in ICI-based therapies for patients with early-stage MMR-D/MSI-H colon and rectal cancer and elaborate on the future treatment paradigm of this unique subgroup of CRC.
Confinement, Environment, and Slave Ships in Early Modern Ocean Voyages
Authors: Harrigan Michael
Published: March 2023

This article explores how onboard sociocultural practices were shaped by different conceptions of human and external environment on seventeenth- and early eighteenth-century French ships embarking for the Indian Ocean basin or across the Atlantic to the Caribbean. In these environments, in which large numbers of people were confined together, physical conditions shaped the sensory and social dynamics of ocean voyages, while they made ships ambiguous sites for the implementation of spiritual practices. Concepts of society responded to a largely unrecognizable marine environment; shipboard conditions of physical confinement were thought conducive to moral disorder, while ships were conceived of as a source of potentially subversive human energies that had to be channeled. These tensions reached a paroxysm on the slave ships increasingly crossing the Atlantic in the seventeenth and eighteenth centuries. The conditions within early modern ships, this article contends, were exacerbated by multiple external factors, making the ship a uniquely unsustainable environment.