bluuebunny/crossref_metadata_2025 huggingface dataset:
Study design and rationale for a cluster randomized trial of a safe child feces management intervention in rural Odisha, India
Authors: Sclar Gloria D. , Bauza Valerie , Mosler Hans-Joachim , Bisoyi Alokananda , Chang Howard H. , Clasen Thomas F.
Published: January 2022

Background

Poor child feces management (CFM) is believed to be an important source of exposure to enteric pathogens that contribute to a large disease burden in low-income settings. While access to sanitation facilities is improving, national surveys indicate that even households with latrines often do not safely dispose of their child’s feces. Working with caregivers in rural Odisha, India, we co-developed an intervention aimed at improving safe disposal of child feces and encouraging child latrine use at an earlier age. We describe the rationale for the intervention and summarize the protocol for a cluster randomized trial (CRT) to evaluate its effectiveness at changing CFM practices.

Methods

The intervention consists of six behavior change strategies together with hardware provision: wash basin and bucket with lid to aid safe management of soiled nappies and a novel latrine training mat to aid safe disposal and latrine training. The intervention will be offered at the village level to interested caregivers of children < 5 years of age by a community-based organization. Following a baseline survey, 74 villages were randomly allocated to either intervention or control arm. The primary outcome is caregiver reported safe disposal of child feces after last defecation, either by the caregiver disposing of the child’s feces into the latrine or the child using the latrine, measured approximately four to six months following intervention delivery. Secondary outcomes include fecal contamination of household drinking water and the childs’ hands. A process evaluation will also be conducted to assess intervention fidelity and reach, and explore implementer and participant feedback.

Discussion

This study addresses a crucial knowledge gap in sanitation by developing a scalable intervention to improve safe management of child feces. The behavior change strategies were designed following the Risks, Attitudes, Norms, Abilities and Self-Regulation (RANAS) approach, which has shown to be effective for other environmental behavior change interventions in low-income settings. The latrine training mat hardware is a novel design developed cooperatively and manufactured locally. The evaluation follows a rigorous CRT study design assessing the impact of the intervention on CFM behavior change, as well as fecal contamination of two sources of potential exposure.

Trial registration

This trial is registered at ISRCTN: ISRCTN15831099.
COVID-19 vaccine hesitancy in the UK: a longitudinal household cross-sectional study
Authors: Chaudhuri Kausik , Chakrabarti Anindita , Chandan Joht Singh , Bandyopadhyay Siddhartha
Published: January 2022

Background

The approved COVID-19 vaccines have shown great promise in reducing disease transmission and severity of outcomes. However, the success of the COVID-19 vaccine rollout is dependent on public acceptance and willingness to be vaccinated. In this study, we aim to examine how the attitude towards public sector officials and the government impact vaccine willingness. The secondary aim is to understand the impact of ethnicity on vaccine-willingness after we explicitly account for trust in public institutions.

Methods

This cross-sectional study used data from a UK population based longitudinal household survey (Understanding Society COVID-19 study, Understanding Society: the UK Household Longitudinal Study) between April 2020-January 2021. Data from 22,421 participants in Waves 6 and 7 of the study were included after excluding missing data. Demographic details in addition to previous survey responses relating to public sector/governmental trust were included as covariates in the main analysis. A logit model was produced to describe the association between public sector/governmental mistrust and the willingness for vaccination with interaction terms included to account for ethnicity/socio-economic status.

Results

In support of existing literature, we identified those from BAME groups were more likely to be unwilling to take the COVID-19 vaccine. We found that positive opinions towards public sector officials (OR 2.680: 95% CI 1.888 – 3.805) and the UK government (OR 3.400; 95% CI 2.454—4.712) led to substantive increase in vaccine willingness. Most notably we identified this effect to vary across ethnicity and socio-economic status with those from South Asian background (OR 4.513; 95% CI 1.012—20.123) and possessing a negative attitude towards public officials and the government being the most unwilling to be vaccinated.

Conclusions

These findings suggests that trust in public sector officials play a key factor in the low vaccination rates particularly seen in at-risk groups. Given the additional morbidity/mortality risk posed by COVID-19 to those from lower socio-economic or ethnic minority backgrounds, there needs to be urgent public health action to review how to tailor health promotion advice given to these groups and examine methods to improve trust in public sector officials and the government.
Links between obesity, weight stigma and learning in adolescence: a qualitative study
Authors: Langford Rebecca , Davies Alisha , Howe Laura , Cabral Christie
Published: January 2022

Background

Educational attainment is a key social determinant of health. Health and education are linked by multiple pathways, many of which are not well understood. One such pathway is the association between being above a healthy weight and lower academic achievement. While various explanations have been put forward to explain this relationship, evidence for causal pathways is sparse and unclear. This study addresses that evidence gap.

Methods

We interviewed 19 adults (late 20s; 14 female, 5 male) and one young person (14 years, male) from the UK in 2019/2020. Participants were recruited from the ALSPAC 1990s birth cohort, sampled to ensure diversity in socio-economic status and educational attainment, and a community-based weight management group for young people. Interviews focused on experiences of being above a healthy weight during secondary school and how this may have affected their learning and achievement. Interviews were face-to-face, digitally recorded, and transcribed verbatim. We analysed the data thematically.

Results

We identified key pathways through which higher body weight may negatively impact educational performance and showed how these are linked within a novel theoretical model. Because larger body size is highly stigmatised, participants engaged in different strategies to minimise their exposure to negative attention. Participants sought to increase their social acceptance or become less socially visible (or a combination of both). A minority navigated this successfully; they often had many friends (or the ‘right’ friends), experienced little or no bullying at school and weight appeared to have little effect on their achievement at school. For most however, the behaviours resulting from these strategies (e.g. disruptive behaviour, truanting, not working hard) or the physical, social or mental impacts of their school experiences (e.g. hungry, tired, self-conscious, depressed) made it difficult to concentrate and/or participate in class, which in turn affected how teachers viewed them.

Conclusions

Action to combat weight stigma, both within schools and in wider society, is urgently required to help address these educational disparities that in turn can impact health in later life.
Reliability of preoperative MRI findings in patients with lumbar spinal stenosis
Authors: Banitalebi Hasan , Espeland Ansgar , Anvar Masoud , Hermansen Erland , Hellum Christian , Brox Jens Ivar , Myklebust Tor Åge , Indrekvam Kari , Brisby Helena , Weber Clemens , Aaen Jørn , Austevoll Ivar Magne , Grundnes Oliver , Negård Anne
Published: January 2022

Background

Magnetic Resonance Imaging (MRI) is an important tool in preoperative evaluation of patients with lumbar spinal stenosis (LSS). Reported reliability of various MRI findings in LSS varies from fair to excellent. There are inconsistencies in the evaluated parameters and the methodology of the studies. The purpose of this study was to evaluate the reliability of the preoperative MRI findings in patients with LSS between musculoskeletal radiologists and orthopaedic spine surgeons, using established evaluation methods and imaging data from a prospective trial.

Methods

Consecutive lumbar MRI examinations of candidates for surgical treatment of LSS from the Norwegian Spinal Stenosis and Degenerative Spondylolisthesis (NORDSTEN) study were independently evaluated by two musculoskeletal radiologists and two orthopaedic spine surgeons. The observers had a range of experience between six and 13 years and rated five categorical parameters (foraminal and central canal stenosis, facet joint osteoarthritis, redundant nerve roots and intraspinal synovial cysts) and one continuous parameter (dural sac cross-sectional area). All parameters were re-rated after 6 weeks by all the observers. Inter- and intraobserver agreement was assessed by Gwet’s agreement coefficient (AC1) for categorical parameters and Intraclass Correlation Coefficient (ICC) for the dural sac cross-sectional area.

Results

MRI examinations of 102 patients (mean age 66 ± 8 years, 53 men) were evaluated. The overall interobserver agreement was substantial or almost perfect for all categorical parameters (AC1 range 0.67 to 0.98), except for facet joint osteoarthritis, where the agreement was moderate (AC1 0.39). For the dural sac cross-sectional area, the overall interobserver agreement was good or excellent (ICC range 0.86 to 0.96). The intraobserver agreement was substantial or almost perfect/ excellent for all parameters (AC1 range 0.63 to 1.0 and ICC range 0.93 to 1.0).

Conclusions

There is high inter- and intraobserver agreement between radiologists and spine surgeons for preoperative MRI findings of LSS. However, the interobserver agreement is not optimal for evaluation of facet joint osteoarthritis.

Trial registration

www.ClinicalTrials.gov identifier: NCT02007083, registered December 2013.
Comprehensive supervised heavy training program versus home training regimen in patients with subacromial impingement syndrome: a randomized trial
Authors: Schydlowsky Pierre , Szkudlarek Marcin , Madsen Ole Rintek
Published: January 2022

Background

There is no consensus on the best training regimen for subacromial impingement syndrome (SIS). Several have been suggested, but never tested.

The purpose of the study is to compare a comprehensive supervised training regimen (STR) based on latest evidence including heavy slow resistance training with a validated home-based regimen (HTR). We hypothesized that the STR would be superior to the HTR.

Methods

Randomised control trial with blinded assessor. 126 consecutive patients with SIS were recruited and equally randomised to 12 weeks of either supervised training regimen (STR), or home-based training regimen (HTR). Primary outcomes were Constant Score (CS) and Shoulder Rating Questionnaire (SRQ) from baseline and 6 months after completed training. Results were analyzed according to intention-to treat principles. The study was retrospectively registered in ClinicalTrials.gov. Date of registration: 07/06/2021. Identification number: NCT04915430.

Results

CS improved by 22.7 points for the STR group and by 23,7 points for the HTR (p = 0.0001). The SRQ improved by 17.7 and 18.1 points for the STR and the HTR groups respectively (p = 0.0001). The inter-group changes were non-significant. All secondary outcomes (passive and active range of motion, pain on impingement test, and resisted muscle tests) improved in both groups, without significant inter-group difference.

Conclusion

We found no significant difference between a comprehensive supervised training regimen including heavy training principles, and a home-based training program in patients with SIS.
Axillary nodal metastasis of operated gallbladder carcinoma: remote site of aggression—a case report
Authors: Vats Manu , Bains Lovenish , Lal Pawan , Mandal Shramana
Published: January 2022

Background

Gallbladder cancer is a very aggressive type of biliary tract cancer. The only curative treatment is complete surgical excision of the tumour. However, even after surgery, there is still a risk of recurrence of the cancer.

Case presentation

A 63-year-old gentleman presented with the complaint of a non-healing ulcer at upper abdomen for the last 1 month. He had undergone a laparoscopic cholecystectomy at a private centre 4 months ago. Investigations confirmed the diagnosis of epigastric port site metastasis from a primary from gall bladder adenocarcinoma. After undergoing completion radical cholecystectomy with wide local excision of the epigastric ulcer, he received 6 cycles of concurrent chemoradiotherapy. Eighteen months later, he presented to us with bilateral axillary swellings. Investigations confirmed isolated bilateral axillary metastasis and the patient underwent a bilateral axillary lymphadenectomy (Level 3). However, PET scan after 6 months showed widespread metastasis and the patient succumbed to the illness 1 month later.

Conclusion

Axillary metastasis probably occurs due to the presence of microscopic systemic metastasis at the time of development of port site metastasis. An R0 resection of the malignancy is the only viable option for effective therapy. The present case highlights the rare involvement of isolated bilateral axillary lymph nodes as a distant metastatic site with no evidence of disease in the locoregional site. However, the prognosis after metastasis remains dismal despite multiple treatment modalities.
Acute kidney injury due to ammonium acid urate stones in a patient with adenovirus gastroenteritis: a case report
Authors: Ban Hideki , Miura Kenichiro , Tomoeda Rika , Hirai Katsuki , Hattori Motoshi
Published: January 2022

Background

Adenovirus gastroenteritis is a common cause of diarrhea and vomiting in infants, resulting in prerenal acute kidney injury (AKI). However, postrenal AKI due to urinary stones associated with adenovirus gastroenteritis is extremely rare. Here, we describe postrenal AKI due to obstructive ammonium acid urate stones associated with adenovirus gastroenteritis.

Case presentation

A previously healthy 6-month-old boy had an 11-day history of severe diarrhea and a 5-day history of vomiting. His stool was positive for adenovirus antigens. We initiated fluid replacement therapy. On the second hospital day, he suddenly developed anuria. Abdominal computed tomography revealed bilateral hydronephrosis, left ureteral stones, and right bladder ureteral junction stones. Laboratory data showed that the creatinine level increased to 1.00 mg/dL. We diagnosed postrenal AKI due to obstructive bilateral urinary stones. Urination with stable urine volume resumed spontaneously after hydration. A few stones were found in the urine, which consisted of ammonium acid urate (> 98%). The serum creatinine level improved to 0.25 mg/dL. He was discharged nine days after admission.

Conclusions

We suggest that adenovirus gastroenteritis be considered in pediatric patients with postrenal AKI due to urinary stones.
Assessing the implementation of a clinical decision support tool in primary care for diabetes prevention: a qualitative interview study using the Consolidated Framework for Implementation Science
Authors: Pratt Rebekah , Saman Daniel M. , Allen Clayton , Crabtree Benjamin , Ohnsorg Kris , Sperl-Hillen JoAnn M. , Harry Melissa , Henzler-Buckingham Hilary , O’Connor Patrick J. , Desai Jay
Published: January 2022

Background

In this paper we describe the use of the Consolidated Framework for Implementation Research (CFIR) to study implementation of a web-based, point-of-care, EHR-linked clinical decision support (CDS) tool designed to identify and provide care recommendations for adults with prediabetes (Pre-D CDS).

Methods

As part of a large NIH-funded clinic-randomized trial, we identified a convenience sample of interview participants from 22 primary care clinics in Minnesota, North Dakota, and Wisconsin that were randomly allocated to receive or not receive a web-based EHR-integrated prediabetes CDS intervention. Participants included 11 clinicians, 6 rooming staff, and 7 nurse or clinic managers recruited by study staff to participate in telephone interviews conducted by an expert in qualitative methods. Interviews were recorded and transcribed, and data analysis was conducted using a constructivist version of grounded theory.

Results

Implementing a prediabetes CDS tool into primary care clinics was useful and well received. The intervention was integrated with clinic workflows, supported primary care clinicians in clearly communicating prediabetes risk and management options with patients, and in identifying actionable care opportunities. The main barriers to CDS use were time and competing priorities. Finally, while the implementation process worked well, opportunities remain in engaging the care team more broadly in CDS use.

Conclusions

The use of CDS tools for engaging patients and providers in care improvement opportunities for prediabetes is a promising and potentially effective strategy in primary care settings. A workflow that incorporates the whole care team in the use of such tools may optimize the implementation of CDS tools like these in primary care settings.

Trial registrationName of the registry: Clinicaltrial.gov. Trial registration number: NCT02759055. Date of registration: 05/03/2016. URL of trial registry record:https://clinicaltrials.gov/ct2/show/NCT02759055Prospectively registered.
Veteran families with complex needs: a qualitative study of the veterans’ support system
Authors: Maguire Angela M. , Keyser Julieann , Brown Kelly , Kivlahan Daniel , Romaniuk Madeline , Gardner Ian R. , Dwyer Miriam
Published: January 2022

Background

Families with complex needs face significant challenges accessing and navigating health and social services. For veteran families, these challenges are exacerbated by interactions between military and civilian systems of care, and the density of the veterans’ non-profit sector. This qualitative study was designed to gather rich, detailed information on complex needs in veteran families; and explore service providers’ and families’ experiences of accessing and navigating the veterans’ support system.

Methods

The study comprised participant background questionnaires (n = 34), focus groups with frontline service providers (n = 18), and one-on-one interviews with veteran families (n = 16) in Australia. The semi-structured focus groups and interviews were designed to gather rich, detailed information on four study topics: (i) health and wellbeing needs in veteran families; (ii) service-access barriers and facilitators; (iii) unmet needs and gaps in service provision; and (iv) practical solutions for improving service delivery. The study recruited participants who could best address the focus on veteran families with complex needs. The questionnaire data was used to describe relevant characteristics of the participant sample. The focus groups and interviews were audio-recorded, transcribed, and a reflexive thematic analysis was conducted to identify patterns of shared meaning in the qualitative data.

Results

Both service providers and families found the veterans’ support system difficult to access and navigate. System fragmentation was perceived to impede care coordination, and delay access to holistic care for veteran families with complex needs. The medico-legal aspects of compensation and rehabilitation processes were perceived to harm veteran identity, and undermine health and wellbeing outcomes. Recovery-oriented practice was viewed as a way to promote veteran independence and self-management. Participants expressed a strong preference for family-centred care that was informed by an understanding of military lifestyle and culture.

Conclusion

The health and wellbeing needs of veteran families intensify during the transition from full-time military service to civilian environments, and service- or reintegration-related difficulties may emerge (or persist) for a significant period of time thereafter. Veteran families with complex needs are unduly burdened by care coordination demands. There is a pressing need for high-quality implementation studies that evaluate initiatives for integrating fragmented systems of care.
Reasons for acute referrals to hospital from general practitioners and out-of-hours doctors in Norway: a registry-based observational study
Authors: Blinkenberg Jesper , Hetlevik Øystein , Sandvik Hogne , Baste Valborg , Hunskaar Steinar
Published: January 2022

Background

General practitioners (GPs) and out-of-hours (OOH) doctors are gatekeepers to acute hospital admissions in many healthcare systems. The aim of the present study was to investigate the whole range of reasons for acute referrals to somatic hospitals from GPs and OOH doctors and referral rates for the most common reasons. We wanted to explore the relationship between some common referral diagnoses and the discharge diagnosis, and associations with patient’s gender, age, and GP or OOH doctor referral.

Methods

A registry-based study was performed by linking national data from primary care in the physicians’ claims database with hospital services data in the Norwegian Patient Registry (NPR). The referring GP or OOH doctor was defined as the physician who had sent a claim for the patient within 24 h prior to an acute hospital stay. The reason for referral was defined as the ICPC-2 diagnosis used in the claim; the discharge diagnoses (ICD-10) came from NPR.

Results

Of all 265,518 acute hospital referrals from GPs or OOH doctors in 2017, GPs accounted for 43% and OOH doctors 57%. The overall referral rate per contact was 0.01 from GPs and 0.11 from OOH doctors, with large variations by referral diagnosis. Abdominal pain (D01) (8%) and chest pain (A11) (5%) were the most frequent referral diagnoses. For abdominal pain and chest pain referrals the most frequent discharge diagnosis was the corresponding ICD-10 symptom diagnosis, whereas for pneumonia-, appendicitis-, acute myocardial infarction- and stroke referrals the corresponding disease diagnosis was most frequent. Women referred with chest pain were less likely to be discharged with ischemic heart disease than men.

Conclusions

The reasons for acute referral to somatic hospitals from GPs and OOH doctors comprise a wide range of reasons, and the referral rates vary according to the severity of the condition and the different nature between GP and OOH services. Referral rates for OOH contacts were much higher than for GP contacts. Patient age, gender and referring service influence the relationship between referral and discharge diagnosis.
Improving hospital-based processes for effective implementation of Government funded health insurance schemes: evidence from early implementation of PM-JAY in India
Authors: Saxena Anurag , Trivedi Mayur , Shroff Zubin Cyrus , Sharma Manas
Published: January 2022

Background

Government-sponsored health insurance schemes (GSHIS) aim to improve access to and utilization of healthcare services and offer financial protection to the population. India’s Ayushman Bharat Pradhan Mantri Jan Arogya Yojana (PM-JAY) is one such GSHIS. This paper aims to understand how the processes put in place to manage hospital-based transactions, from the time a beneficiary arrives at the hospital to discharge are being implemented in PM-JAY and how to improve them to strengthen the scheme’s operation.

Methods

Guidelines were reviewed for the processes associated with hospital-based transactions, namely, beneficiary authentication, treatment package selection, preauthorization, discharge, and claims payments. Across 14 hospitals in Gujarat and Madhya Pradesh states, the above-mentioned processes were observed, and using a semi-structured interview guide fifty-three respondents were interviewed. The study was carried out from March 2019 to August 2019.

Results

Average turn-around time for claim reimbursement is two to six times higher than that proposed in guidelines and tender. As opposed to the guidelines, beneficiaries are incurring out-of-pocket expenditure while availing healthcare services. The training provided to the front-line workers is software-centric. Hospital-based processes are relatively more efficient in hospitals where frontline workers have a medical/paramedical/managerial background.

Conclusions

There is a need to broaden capacity-building efforts from enabling frontline staff to operate the scheme’s IT platform to developing the technical, managerial, and leadership skills required for them. At the hospital level, an empowered frontline worker is the key to efficient hospital-based processes. There is a need to streamline back-end processes to eliminate the causes for delay in the processing of claim payment requests. For policymakers, the most important and urgent need is to reduce out-of-pocket expenses. To that end, there is a need to both revisit and streamline the existing guidelines and ensure adherence to the guidelines.
Isolation, antimicrobial susceptibility patterns, and risk factors assessment of non-typhoidal Salmonella from apparently healthy and diarrheic dogs
Authors: Usmael Belisa , Abraha Bruk , Alemu Sisay , Mummed Bahar , Hiko Adem , Abdurehman Abdallahi
Published: January 2022

Background

Dogs are one of the important asymptomatic carriers of antimicrobial resistant and potentially pathogenic strains of Salmonella. They can harbor large bacterial load in the intestines and mesenteric lymph nodes which can be shed in their feces with the possibility of transmission to humans. Therefore, a cross-sectional study was conducted with the objectives of estimating the prevalence of non-typhoidal Salmonella, assessing the risk factors for dog’s Salmonella carriage, and profiling the antimicrobial resistance pattern of Salmonella isolates among housed dogs in Harar town, Eastern Ethiopia. A total of 415 rectal swab samples were collected from randomly selected dogs. Samples were examined for non-typhoidal Salmonella using standard bacteriologic culture and biochemical tests. The disk diffusion method (Kirby-Bauer test) was employed to evaluate the isolates for their susceptibility against five antimicrobials.

Results

Non-typhoidal Salmonella were isolated from 26 (6.3%) of the rectal swab samples, with significantly higher occurrence in diarrheic (15.2%) than non-diarrheic (5.5%) dogs. The risk of Salmonella harboring was significantly higher in female dogs than in male dogs (OR = 2.5, p = 0.027). Dogs fecal shedding of Salmonella was relatively higher in households who used offal as a main feed type for their dogs (23.1%; 95% CI = 5–53.8) than those who used leftover food (10.1%; 95% CI = 5.7–16.1) and practiced mixed feeding system (17%; 95% CI = 7.6–30.8). Salmonella isolates showed higher resistance to ampicillin (41.7%), while all isolates were fully susceptible to gentamicin. Moreover, 58.3% of Salmonella isolates showed resistance to at least one of the tested antimicrobials. Majorities (72.7%) of the dog owners had no awareness on the risk of zoonotic salmonellosis from dog and all of the respondents use bare hand to clean dog kennel.

Conclusion

Our study reveals the importance of both diarrheic and apparently healthy housed dogs in the harboring and shedding of antimicrobial resistant non-typhoidal Salmonella. The risk of non-typhoidal Salmonella spread among pet owners is not negligible, especially in households who use offal as main feed type. Therefore, an integrated approach such as: proper dog handling practices; continuous evaluation of antimicrobial resistance; and rational use of antimicrobials in the field of veterinary sector are necessary to tackle the problem.
Causes of admission and outcomes of brown hare (Lepus europaeus) leverets at wildlife rescue centres in the Czech Republic
Authors: Lukesova Gabriela , Voslarova Eva , Vecerek Vladimir , Nenadovic Katarina
Published: January 2022

Background

Wildlife rescue centres care for orphaned and injured young as an integral part of their work. However, inappropriate interventions in nature can have a negative effect on the survival of young hares, especially when the care of these young is not very successful. The aim of this study was to assess the number of brown hare leverets admitted to rescue centres in the Czech Republic in the period from 2010 to 2019, the causes of their admission to rescue centres and their outcomes.

Results

We evaluated the number of brown hare leverets admitted to rescue centres in the Czech Republic in the period from 2010 to 2019 and the outcomes associated with their leaving these rescue centres. We found that the number of brown hare leverets admitted increased during the monitored period (rSp = 0.6364, p < 0.05). The most frequent reasons for admission were the admission of orphaned young (49.15%), leverets brought needlessly (19.60%) and leverets that had been bitten by other animals (18.63%). More (p < 0.05) young admitted to rescue centres died (40.76%) than were reared successfully and released back into the wild (32.40%). Leverets that had been caught needlessly or orphaned and late-born leverets survived and could be released back into the wild (38.56, 34.51 and 52%, respectively), while fatalities were recorded in most leverets bitten by another animal (65.05%) or hit in a collision with a vehicle (97.06%). Most young hares (76.92%) that were exhausted or starved at the time of admission could not be saved.

Conclusions

Since only a small proportion of hares in a litter survive until adulthood in the wild, young animals being found and taken needlessly to rescue centres may harm the hare population. Our results show that only around one in three healthy young hares admitted to rescue centres are reared successfully. It is, in our opinion, of fundamental importance to the protection of brown hare leverets to inform the public of this issue and prevent needless interventions into natural rearing in the wild.
Risk factors for cranial cruciate ligament rupture in dogs participating in canine agility
Authors: Sellon Debra C. , Marcellin-Little Denis J.
Published: January 2022

Background

Cranial cruciate ligament rupture (CCLR) is one of the most common causes of pelvic limb lameness in dogs. Risk factors for CCLR include breed (especially large and giant breeds), body weight, gender and spay/neuter status, and age. Few studies have evaluated physical activity and fitness indicators, however, as risk factors for disease. This study used an online questionnaire distributed primarily via social media to assess risk factors for CCLR in dogs actively engaged in agility training or competition to determine demographic and physical activity factors associated with rupture.

Results

Data from 260 dogs with CCLR were compared to similar data from 1006 dogs without CCLR. All dogs were actively training or competing in agility at the time of CCLR or the time of data submission, respectively. Physical characteristics associated with increased risk of CCLR included younger age, spayed female sex, greater body weight, and greater weight to height ratio. Agility activities associated with increased odds ratios included competition in events sponsored by the North American Dog Agility Council (NADAC), competing at novice and intermediate levels, and competing in fewer than 10 events/year. Odds ratios were lower in dogs that competed in events sponsored by United Kingdom Agility International (UKI). Other activities associated with increased odds ratio for CCLR included involvement in flyball activities and short walks or runs over hilly or flat terrain on a weekly basis. Activities associated with decreased odds ratio included involvement in dock diving, barn hunt, nosework, or lure coursing/racing activities and participation in core balance and strength exercises at least weekly.

Conclusions

These results are consistent with previous studies demonstrating that body weight and spay/neuter status are risk factors for CCLR in dogs. This is the first report to demonstrate that risk of CCLR in agility dogs is decreased in dogs that engage in regular core strengthening exercises, compete more frequently, compete at higher levels, and compete in more athletically challenging venues.
Analysis of genetic variants in myeloproliferative neoplasms using a 22-gene next-generation sequencing panel
Authors: Tan Jaymi , Chow Yock Ping , Zainul Abidin Norziha , Chang Kian Meng , Selvaratnam Veena , Tumian Nor Rafeah , Poh Yang Ming , Veerakumarasivam Abhi , Laffan Michael Arthur , Wong Chieh Lee
Published: January 2022

Background

The Philadelphia (Ph)-negative myeloproliferative neoplasms (MPNs), namely essential thrombocythaemia (ET), polycythaemia vera (PV) and primary myelofibrosis (PMF), are a group of chronic clonal haematopoietic disorders that have the propensity to advance into bone marrow failure or acute myeloid leukaemia; often resulting in fatality. Although driver mutations have been identified in these MPNs, subtype-specific markers of the disease have yet to be discovered. Next-generation sequencing (NGS) technology can potentially improve the clinical management of MPNs by allowing for the simultaneous screening of many disease-associated genes.

Methods

The performance of a custom, in-house designed 22-gene NGS panel was technically validated using reference standards across two independent replicate runs. The panel was subsequently used to screen a total of 10 clinical MPN samples (ET n = 3, PV n = 3, PMF n = 4). The resulting NGS data was then analysed via a bioinformatics pipeline.

Results

The custom NGS panel had a detection limit of 1% variant allele frequency (VAF). A total of 20 unique variants with VAFs above 5% (4 of which were putatively novel variants with potential biological significance) and one pathogenic variant with a VAF of between 1 and 5% were identified across all of the clinical MPN samples. All single nucleotide variants with VAFs ≥ 15% were confirmed via Sanger sequencing.

Conclusions

The high fidelity of the NGS analysis and the identification of known and novel variants in this study cohort support its potential clinical utility in the management of MPNs. However, further optimisation is needed to avoid false negatives in regions with low sequencing coverage, especially for the detection of driver mutations in MPL.
Securin overexpression correlates with the activated Rb/E2F1 pathway and histone H3 epigenetic modifications in raw areca nut-induced carcinogenesis in mice
Authors: Boruah Nabamita , Singh Chongtham Sovachandra , Swargiary Pooja , Dkhar Hughbert , Chatterjee Anupam
Published: January 2022

Background

Raw areca nut (RAN) consumption induces oral, esophageal and gastric cancers, which are significantly associated with the overexpression of pituitary tumor transforming gene 1/securin and chromosomal instability (CIN). An association of Securin/PTTG1 upregulation and gastric cancer in human was also demonstrated earlier. Since the molecular mechanism underlying securin upregulation remains unclear, this study intended to investigate the association of securin upregulation with the Rb-E2F1 circuit and epigenetic histone (H3) modification patterns both globally and in the promoter region of the securin gene.

Methods

Six groups of mice were used, and in the treated group, each mouse consumed 1 mg of RAN extract with lime per day ad libitum in the drinking water for 60 days, after which the dose was increased by 1 mg every 60 days. Histopathological evaluation of stomach tissues was performed and securin expression was analysed by immunoblotting as well as by immunohistochemistry. ChIP-qPCR assays were performed to evaluate the recruitment of different histone modifications in the core promoter region of securin gene as well as its upstream and downstream regions.

Results

All mice developed gastric cancer with securin overexpression after 300 days of feeding. Immunohistochemistry data revealed hyperphosphorylation of Rb and upregulation of E2F1 in the RAN-treated samples. Increased trimethylation of H3 lysine 4 and acetylation of H3 lysine 9 and 18 both globally and in the promoter region of the securin gene were observed by increasing the levels of lysine-N-methyltransferase 2A, lysine-acetyltransferase, EP-300 and PCAF after RAN treatment. ChIP-qPCR data revealed that the quantity of DNA fragments retrieved from the immunoprecipitated samples was maximum in the -83 to -192 region than further upstream and the downstream of the promoter for H3K4Me3, H3K9ac, H3K18ac and H3K9me3.

Conclusions

RAN-mediated pRb-inactivation induced securin upregulation, a putative E2F1 target, by inducing misregulation in chromatin remodeling in its promoter region, which led to transcriptional activation and subsequent development of chromosomal instability. Therefore, present results have led to the hypothesis that RAN-induced changes in the epigenetic landscape, securin overexpression and subsequent elevation of chromosomal instability is probably byproducts of inactivation of the pRb pathway.
The Prognostic value of the Fibrinogen to pre-albumin ratio in malignant tumors of the digestive system: a systematic review and meta-analysis
Authors: Li Baibei , Deng Huachu , Zhou Ziyan , Tang Bo
Published: January 2022

Background

In recent years, the Fibrinogen to pre-albumin ratio (FPR) has been reported in many studies to be significantly associated with the prognosis of various cancers. This systematic review and meta-analysis aimed to investigate the prognostic value of FPR in malignant tumors of the digestive system based on available evidence.

Methods

The relevant articles published before July 1, 2021, were systematically retrieved from electronic databases to evaluate the effect of Fibrinogen to pre-albumin ratio (FPR) on the prognosis of patients with malignant digestive system tumors and calculate the hazard ratio (HR) and the corresponding 95% confidence interval (CI).

Result

Thirteen articles, all from China, including 15 cohort studies and a total of 5116 cases, were included in this study. A high FPR was associated with poor overall survival (HR = 1.88, 95%CI 1.53–2.32, P < 0.001), recurrence-free survival (HR = 2.29, 95%CI 1.91–2.76, P < 0.001), progression-free survival (HR = 1.96, 95%CI: 1.33–2.90, P = 0.001), complications (HR = 1.78, 95%CI: 1.06–3.00, P = 0.029), disease-free survival (HR = 1.46, 95%CI: 1.08–1.97, P = 0.013) was significantly associated with cancer-specific survival (HR = 1.44, 95%CI: 1.15–1.79, P = 0.001). Even though intergroup differences were present, FPR was strongly associated with overall and relapse-free survival, and sensitivity analysis suggested that our results were stable.

Conclusion

FPR can be used as a valuable indicator to predict the prognosis of patients with malignant digestive system tumors.
SHC4 promotes tumor proliferation and metastasis by activating STAT3 signaling in hepatocellular carcinoma
Authors: Zhang Xin , Zhang Hongwei , Liao Zhibin , Zhang Jiacheng , Liang Huifang , Wang Weixing , Yu Jia , Dong Keshuai
Published: January 2022

Background

The Src homology and collagen 4 (SHC4) is an important intracellular adaptor protein that has been shown to play a pro-cancer role in melanoma and glioma. However, the biological function and detailed mechanisms of SHC4 in hepatocellular carcinoma progression are unclear. This study aimed to evaluate the potential prognostic and treatment value of SHC4 in patients with HCC.

Methods

The expression status of SHC4 in HCC tissues were investigated by immunohistochemistry and western blotting. Clinical significance of SHC4 was evaluated in a large cohort of HCC patients. The effects of SHC4 repression or overexpression on migration, invasion, and tumor growth were detected by colony formation assay, wound healing, transwell assays, and xenograft assay. Cell cycle and EMT-related proteins were detected by western blotting and immunofluorescence. In addition, the molecular regulation between SHC4 and STAT3 signaling in HCC were discovered by western blotting, immunofluorescence and xenograft assay.

Results

SHC4 was overexpressed in HCC compared to adjacent normal liver tissues and increased SHC4 expression was associated with high AFP level, incomplete tumor encapsulation, poor tumor differentiation and poor prognosis. SHC4 was shown to enhance cell proliferation, colony formation, cells migration and invasion in vitro, and promotes cell cycle progression and EMT process in HCC cells. Tumor xenograft model assay confirmed the oncogenic role of SHC4 in tumorigenicity in nude mice. Moreover, activation of STAT3 signaling was found in the SHC4 overexpressed HCC cells and HCC tissues. Further intervention of STAT3 confirmed STAT3 as an important signaling pathway for the oncogenic role of SHC4 in HCC.

Conclusions

Together, our results reveal that SHC4 activates STAT3 signaling to promote HCC progression, which may provide new clinical ideas for the treatment of HCC.
MiR-937-3p promotes metastasis and angiogenesis and is activated by MYC in lung adenocarcinoma
Authors: Ma Zijian , Chen Ganyi , Chen Yiqian , Guo Zizhang , Chai Hao , Tang Yu , Zheng Lin , Wei Ke , Pan Chunfeng , Ma Zhifei , Xia Yang , Zhang Aiping
Published: January 2022

Background

Non-small cell lung cancer (NSCLC) is still one of the diseases with the highest mortality and morbidity, and lung adenocarcinoma (LUAD) accounts for more than half of all NSCLC cases in most countries. miRNA can be used as a potential biological marker and treatment for lung adenocarcinoma. However, the effect of miR-937-3p to the invasion and metastasis of LUAD cells is not clear.

Methods

miRNA microarray is used to analyze the expression of miRNA in lung adenocarcinoma tissue. Transwell migration, Wound-healing assay and Western blot analysis are used to analyze cell migration, invasion and epithelial-mesenchymal transition (EMT) capabilities. Tube formation is used to assess angiogenesis ability. In addition, dual luciferase reporter gene detection is used to identify the potential binding between miRNA and target mRNA. In vivo experiments were performed on male NOD/SCID nude mice by tail vein injection to establish a transplanted tumor model. The CHIP experiment is used to verify the transcription factors of miRNA.

Result

In our study, miR-937-3p was high-regulated in LUAD cell lines and tissues, and its expression level was related to tumor progression. We found that miR-937-3p high-expression has an effect on cell invasion and metastasis. In molecular mechanism, miR-937-3p causes SOX11 reduction by directly binding to the 3′-UTR of SOX11.In addition, MYC affects miR-937-3p transcription by binding to its promoter region.

Conclusions

Our research shows that miR-937-3p is mediated by MYC and can control the angiogenesis, invasion and metastasis of LUAD by regulating SOX11, thereby promoting the progress of LUAD. We speculate that miR-937-3p can be used as a therapeutic target and potential biomarker for LUAD.
hsa_circ_0000231 Promotes colorectal cancer cell growth through upregulation of CCND2 by IGF2BP3/miR-375 dual pathway
Authors: Zhang Wei , Wang Bo , Lin Yilin , Yang Yang , Zhang Zhen , Wang Quan , Zhang Haoran , Jiang Kewei , Ye Yingjiang , Wang Shan , Shen Zhanlong
Published: January 2022

Background

Circular RNAs (circRNAs) have emerged as vital regulators of the initiation and progression of diverse kinds of human cancers. In this study, we explored the role of hsa_circ_0000231 and its downstream pathway in CRC.

Methods

The expression profile of circRNAs in 5 pairs of CRC tissues and adjacent normal tissues were analyzed by Microarray. Quantitative real-time PCR and in situ hybridization and Base Scope Assay were used to determine the level and prognostic values of hsa_circ_0000231. Then, functional experiments in vitro and in vivo were performed to investigate the effects of hsa_circ_0000231 on cell proliferation. Mechanistically, fluorescent in situ hybridization, dual luciferase reporter assay, RNA pull-down and RNA immunoprecipitation experiments were performed to confirm the interaction between hsa_circ_0000231 and IGF2BP3 or has_miR-375.

Results

We acquired data through circRNA microarray profiles, showing that the expression of hsa_circ_0000231 was upregulated in CRC primary tissues compared to adjacent normal tissues, which was indicated poor prognosis of patients with CRC. Functional analysis indicated that inhibition of hsa_circ_0000231 in CRC cell lines could suppress CRC cell proliferation as well as tumorigenesis in vitro and in vivo. The mechanistic analysis showed that hsa_circ_0000231 might, on the one hand, act as a competing endogenous RNA of miR-375 to promote cyclin D2 (CCND2) and, on the other hand, bind to the IGF2BP3 protein to prevent CCND2 degradation.

Conclusions

The findings suggested that hsa_circ_0000231 facilitated CRC progression by sponging miR-375 or binding to IGF2BP3 to modulate CCND2, implying that hsa_circ_0000231 might be a potential new diagnostic and therapeutic biomarker of CRC.
Molecular identification and anti-malarial drug resistance profile of Plasmodium falciparum from patients attending Kisoro Hospital, southwestern Uganda
Authors: Manirakiza Godfrey , Kassaza Kennedy , Taremwa Ivan Mugisha , Bazira Joel , Byarugaba Fredrick
Published: January 2022

Background

The evolution of malaria infection has necessitated the development of highly sensitive diagnostic assays, as well as the use of dried blood spots (DBS) as a potential source of deoxyribonucleic acid (DNA) yield for polymerase chain reaction (PCR) assays. This study identified the different Plasmodium species in malaria-positive patients, and the anti-malarial drug resistance profile for Plasmodium falciparum using DBS samples collected from patients attending Kisoro Hospital in Kisoro district, Southwestern Uganda.

Methods

The blood samples were prospectively collected from patients diagnosed with malaria to make DBS, which were then used to extract DNA for real-time PCR and high-resolution melting (HRM) analysis. Plasmodium species were identified by comparing the control and test samples using HRM-PCR derivative curves. Plasmodium falciparum chloroquine (CQ) resistance transporter (pfcrt) and kelch13 to screen the samples for anti-malarial resistance markers. The HRM-PCR derivative curve was used to present a summary distribution of the different Plasmodium species as well as the anti-malarial drug profile.

Results

Of the 152 participants sampled, 98 (64.5%) were females. The average age of the participants was 34.9 years (range: 2 months–81 years). There were 134 samples that showed PCR amplification, confirming the species as Plasmodium. Plasmodium falciparum (N = 122), Plasmodium malariae (N = 6), Plasmodium ovale (N = 4), and Plasmodium vivax (N = 2) were the various Plasmodium species and their proportions. The results showed that 87 (71.3%) of the samples were sensitive strains/wild type (CVMNK), 4 (3.3%) were resistant haplotypes (SVMNT), and 31 (25.4%) were resistant haplotypes (CVIET). Kelch13 C580Y mutation was not detected.

Conclusion

The community served by Kisoro hospital has a high Plasmodium species burden, according to this study. Plasmodium falciparum was the dominant species, and it has shown that resistance to chloroquine is decreasing in the region. Based on this, molecular identification of Plasmodium species is critical for better clinical management. Besides, DBS is an appropriate medium for DNA preservation and storage for future epidemiological studies.