bluuebunny/crossref_metadata_2025 huggingface dataset:
Airway Consideration in Maxillofacial Trauma
Authors: Singh Pallav , Mishra Prabhat , Tiwari Tanmay , Singh Gyan Prakash
Published: June 2022

Management of airway is the most important concern in critically injured patient with life-threatening injuries for an anesthesiologist as well as primary caregiver as it may distort airway anatomy as well as destabilize the cervical spine. These patients are potentially difficult candidates for mask ventilation and endotracheal intubation. Additionally, these patients are prone to regurgitation as they may have full stomach condition. The requirement of maxillofacial surgery is free access to the oral cavity; thus, securing alternate methods to maintain a safe airway is the primary priority. To improve the clinical outcome of these patients, there should be mutual cooperation between the anesthesiologist, maxillofacial surgeon, and ENT surgeon (for emergency tracheostomy, if needed). In this review, we are discussing primary management in emergency, relevant anatomy, difficulty in securing patent airway, and possible approach for airway management in maxillofacial trauma patients.
A Successful Medical Management of Enterococcal Endocarditis Presenting as Cellulitis
Authors: Kataria Riya , Senthil N. , Lakshmanan Suja , Anil Archa Anna
Published: June 2022

Infective endocarditis is an infection commonly caused by bacterial pathogens and is known to affect intracardiac structures. We herein report a previously healthy man who presented with complications of infective endocarditis caused by Enterococcal faecalis and was further managed with appropriate antibiotics without the needed surgical interventions.
Experiences of Musical Improvisation: Self-Individuation and Participatory Sense-Making
Authors: Lanier Mary Ann
Published: June 2022

Improvisation is an important element of global musical practices. However, musical improvisation is often neglected in K-12 and collegiate music education programs, with some music educators suggesting that improvisation cannot be taught. Rather, improvisation must be facilitated, enabled, and fostered. In this review of literature, I examined musicians’ experiences when improvising to provide information about the characteristics of the environment needed to foster student improvisation. I drew upon recent developments in music perception and cognition studies to frame a view of individual and group processes in improvisation, and I suggest steps teachers can take to facilitate improvisation in music education settings.
Assessment of systemic and gastrointestinal tissue damage biomarkers for GVHD risk stratification
Authors: Etra Aaron , Gergoudis Stephanie , Morales George , Spyrou Nikolaos , Shah Jay , Kowalyk Steven , Ayuk Francis , Baez Janna , Chanswangphuwana Chantiya , Chen Yi-Bin , Choe Hannah , DeFilipp Zachariah , Gandhi Isha , Hexner Elizabeth , Hogan William J. , Holler Ernst , Kapoor Urvi , Kitko Carrie L. , Kraus Sabrina , Lin Jung-Yi , Al Malki Monzr , Merli Pietro , Pawarode Attaphol , Pulsipher Michael A. , Qayed Muna , Reshef Ran , Rösler Wolf , Schechter Tal , Van Hyfte Grace , Weber Daniela , Wölfl Matthias , Young Rachel , Özbek Umut , Ferrara James L. M. , Levine John E.
Published: June 2022

We used a rigorous PRoBE (prospective-specimen collection, retrospective-blinded-evaluation) study design to compare the ability of biomarkers of systemic inflammation and biomarkers of gastrointestinal (GI) tissue damage to predict response to corticosteroid treatment, the incidence of clinically severe disease, 6-month nonrelapse mortality (NRM), and overall survival in patients with acute graft-versus-host disease (GVHD). We prospectively collected serum samples of newly diagnosed GVHD patients (n = 730) from 19 centers, divided them into training (n = 352) and validation (n = 378) cohorts, and measured TNFR1, TIM3, IL6, ST2, and REG3α via enzyme-linked immunosorbent assay. Performances of the 4 strongest algorithms from the training cohort (TNFR1 + TIM3, TNFR1 + ST2, TNFR1 + REG3α, and ST2 + REG3α) were evaluated in the validation cohort. The algorithm that included only biomarkers of systemic inflammation (TNFR1 + TIM3) had a significantly smaller area under the curve (AUC; 0.57) than the AUCs of algorithms that contained ≥1 GI damage biomarker (TNFR1 + ST2, 0.70; TNFR1 + REG3α, 0.73; ST2 + REG3α, 0.79; all P < .001). All 4 algorithms were able to predict short-term outcomes such as response to systemic corticosteroids and severe GVHD, but the inclusion of a GI damage biomarker was needed to predict long-term outcomes such as 6-month NRM and survival. The algorithm that included 2 GI damage biomarkers was the most accurate of the 4 algorithms for all endpoints.
Addition of romiplostim to conditioning prior to HSCT allows chemotherapy reduction while maintaining engraftment levels
Authors: Wilk C. Matthias , Kovtonyuk Larisa V. , Manz Markus G.
Published: June 2022

Allogeneic hematopoietic stem cell transplantation (HSCT) offers a curative treatment approach for certain benign and malignant hematologic diseases. The actual HSCT is preceded by a conditioning therapy that reduces host-vs-HSCT graft rejection and creates niche space for transplanted hematopoietic stem and progenitor cells (HSPCs). Conditioning consists of chemotherapy with or without irradiation and is a major cause of side effects in HSCT. However, reduction of the intensity of cytotoxic conditioning leads to higher rates of engraftment failure and increased rates of relapse. We here tested if the addition of an HSC cycling inducing agent during conditioning allows to diminish the dose of conditioning drugs without reducing subsequent transplanted HSC engraftment in a mouse HSCT model. The thrombopoietin receptor agonist romiplostim was shown to induce cell cycling activity in hematopoietic stem cells (HSCs). We thus tested if the addition of romiplostim to the clinically applied conditioning chemotherapy regimen cyclophosphamide and busulfan leads to increased efficacy of the chemotherapeutic regimen. We found that romiplostim not only sensitizes HSCs to chemotherapy but also enables a reduction of the main chemotherapeutic component busulfan by half while HSC engraftment levels are maintained in long-term, serial transplantation assays.
Phase 2 trial of ixazomib, cyclophosphamide, and dexamethasone for previously untreated light chain amyloidosis
Authors: Muchtar Eli , Gertz Morie A. , LaPlant Betsy R. , Buadi Francis K. , Leung Nelson , O’Brien Patrick , Bergsagel P. Leif , Fonder Amie , Hwa Yi Lisa , Hobbs Miriam , Helgeson Dania K. , Bradt Erin E. , Gonsalves Wilson , Lacy Martha Q. , Kapoor Prashant , Siddiqui Mustaqueem , Larsen Jeremy T. , Warsame Rahma , Hayman Suzanne R. , Go Ronald S. , Dingli David , Kourelis Taxiarchis V. , Dispenzieri Angela , Rajkumar S. Vincent , Kumar Shaji K.
Published: June 2022

Bortezomib, a proteasome inhibitor (PI), has shown efficacy in the treatment of newly diagnosed and relapsed light chain (AL) amyloidosis, and is often used in combination with cyclophosphamide and dexamethasone. Ixazomib is the first oral PI to be approved in routine practice but has not yet been evaluated in the upfront treatment setting. Newly diagnosed AL amyloidosis patients with measurable disease and adequate organ function were enrolled. The primary objective was to determine the hematologic response rate of ixazomib in combination with cyclophosphamide and dexamethasone. Treatment was given for 12 cycles, followed by ixazomib maintenance until progression. Thirty-five patients were included; their median age was 67 years, and 69% were male. Major organ involvement included heart (66%) and kidneys (54%). A median of 4 induction cycles (range, 1-12) were administered. The overall hematologic response to induction was 63% and included complete response in 11.4% and very good partial response in 37.1% of patients. One patient was upstaged to complete response during maintenance. The most common reason for going off study was the institution of alternate therapy (61%). With a median follow-up of 29.7 months for the living patients, the 2-year progression-free survival and overall survival were 74% and 78%, respectively. The median time to alternate therapy was 7.5 months. Grade ≥3 hematologic and nonhematologic adverse events occurred in 23% and 49% of patients. Given ixazomib’s favorable toxicity profile, which is an important advantage for the typically frail AL population, further evaluation of ixazomib in other combinations in the upfront setting is warranted. This trial was registered at www.clinicaltrials.gov as #NCT01864018.
Bronchiolitis obliterans syndrome after lung or haematopoietic stem cell transplantation: current management and future directions
Authors: Glanville Allan R. , Benden Christian , Bergeron Anne , Cheng Guang-Shing , Gottlieb Jens , Lease Erika D. , Perch Michael , Todd Jamie L. , Williams Kirsten M. , Verleden Geert M.
Published: June 2022

Bronchiolitis obliterans syndrome (BOS) may develop after either lung or haematopoietic stem cell transplantation (HSCT), with similarities in histopathological features and clinical manifestations. However, there are differences in the contributory factors and clinical trajectories between the two conditions. BOS after HSCT occurs due to systemic graft-versus-host disease (GVHD), whereas BOS after lung transplantation is limited to the lung allograft. BOS diagnosis after HSCT is more challenging, as the lung function decline may occur due to extrapulmonary GVHD, causing sclerosis or inflammation in the fascia or muscles of the respiratory girdle. Treatment is generally empirical with no established effective therapies. This review provides rare insights and commonalities of both conditions, which are not well elaborated elsewhere in contemporary literature, and highlights the importance of cross disciplinary learning from experts in other transplant modalities. Treatment algorithms for each condition are presented, based on the published literature and consensus clinical opinion. Immunosuppression should be optimised, and other conditions or contributory factors treated where possible. When initial treatment fails, the ultimate therapeutic option is lung transplantation (or re-transplantation in the case of BOS after lung transplantation) in carefully selected candidates. Novel therapies under investigation include aerosolised liposomal cyclosporine, Janus kinase inhibitors, antifibrotic therapies and (in patients with BOS after lung transplantation) B-cell-directed therapies. Effective novel treatments that have a tangible impact on survival and thereby avoid the need for lung transplantation or re-transplantation are urgently required.
Multidisciplinary care in chronic airway diseases: the Newcastle model
Authors: McDonald Vanessa M. , Harrington John , Clark Vanessa L. , Gibson Peter G.
Published: June 2022

Chronic airway diseases including asthma and COPD are prevalent and high-burden conditions with the majority of patients successfully managed in the primary care setting. However, for some patients with more complex disease such as difficult-to-treat or severe asthma, or complex COPD, tertiary care is required. This review provides an overview of the successful tertiary care multidisciplinary respiratory service that operates in Newcastle, New South Wales, Australia, which has been integrated into the tertiary care outpatient clinics for almost three decades. The service is multifaceted in terms of the clinical care it provides; it includes an “Inpatient Service”, “Asthma Management Service”, “Difficult Airways Clinic”, “Drug Administration Clinic”, “Rapid Access Clinic” and “Pulmonary Rehabilitation”, and has an integrated research programme. The core of the multidisciplinary approach to airway diseases is a person-centred model of care, the “Treatable Traits” approach. The staffing of this service comprises consultant physicians, respiratory advanced trainees, respiratory scientists, physiotherapists, speech pathologists, nurse specialists and a nurse consultant. Patients that present to this service undergo an initial assessment and clinical review by team members, synthesis of relevant data, and development of a diagnosis and management plan. Based on this clinical review, specific interventions are determined according to the traits identified. Over time the service has evolved to accommodate the increasing numbers of patients requiring access to the Difficult Airways Clinic assessment and therapies. This has been facilitated by partnering with the Centres of Excellence in Severe Asthma and Treatable Traits to develop educational and practice management tools.
Hypercontractile esophagus responsive to potassium-competitive acid blockers: a case report
Authors: Shao Yuyang , Xie Chen , Feng Huang , Yan Donglin , Chen Weichang
Published: June 2022

Background

Hypercontractile esophagus is a rare hypercontractile esophageal motility disorder. The etiology of hypercontractile esophagus is unknown but an association between acid reflux and hypercontractile esophagus has been suggested. We present the first report on the use of potassium-competitive acid blockers in the treatment of hypercontractile esophagus.

Case presentation

A 43-year-old man presented with dysphagia, chest pain and regurgitation for a period of 1 year. Initial workup showed a twisted lumen with abnormal contractions in the distal esophagus during upper gastrointestinal endoscopy and abnormal acid exposure under 24-h esophageal pH monitoring. The use of standard-dose proton pump inhibitors didn’t relieve his symptoms. Subsequent high-resolution esophageal manometry made a diagnosis of hypercontractile esophagus. Treatment with vonoprazan resulted in symptomatic resolution and abnormal contractions were no longer detected on follow-up high-resolution manometry.

Conclusions

Potassium-competitive acid blockers like vonoprazan offer an alternative therapeutic method for patients with hypercontractile esophagus who are refractory to proton pump inhibitor therapy. The use of potassium-competitive acid blockers in hypercontractile esophagus warrants further research and may provide evidence for an acid-related etiology of hypercontractile esophagus.
Pre-diagnostic C-reactive protein concentrations, CRP genetic variation and mortality among individuals with colorectal cancer in Western European populations
Authors: Nimptsch Katharina , Aleksandrova Krasimira , Fedirko Veronika , Jenab Mazda , Gunter Marc J. , Siersema Peter D. , Wu Kana , Katzke Verena , Kaaks Rudolf , Panico Salvatore , Palli Domenico , May Anne M , Sieri Sabina , Bueno-de-Mesquita Bas , Standahl Karina , Sánchez Maria-Jose , Perez-Cornago Aurora , Olsen Anja , Tjønneland Anne , Bonet Catalina Bonet , Dahm Christina C. , Chirlaque María-Dolores , Fiano Valentina , Tumino Rosario , Gurrea Aurelio Barricarte , Boutron-Ruault Marie-Christine , Menegaux Florence , Severi Gianluca , van Guelpen Bethany , Lee Young-Ae , Pischon Tobias
Published: June 2022

Background

The role of elevated pre-diagnostic C-reactive protein (CRP) concentrations on mortality in individuals with colorectal cancer (CRC) remains unclear.

Methods

We investigated the association between pre-diagnostic high-sensitivity CRP concentrations and CRP genetic variation associated with circulating CRP and CRC-specific and all-cause mortality based on data from 1,235 individuals with CRC within the European Prospective Investigation into Cancer and Nutrition cohort using multivariable-adjusted Cox proportional hazards regression.

Results

During a median follow-up of 9.3 years, 455 CRC-specific deaths were recorded, out of 590 deaths from all causes. Pre-diagnostic CRP concentrations were not associated with CRC-specific (hazard ratio, HR highest versus lowest quintile 0.92, 95% confidence interval, CI 0.66, 1.28) or all-cause mortality (HR 0.91, 95% CI 0.68, 1.21). Genetic predisposition to higher CRP (weighted score based on alleles of four CRP SNPs associated with higher circulating CRP) was not significantly associated with CRC-specific mortality (HR per CRP-score unit 0.95, 95% CI 0.86, 1.05) or all-cause mortality (HR 0.98, 95% CI 0.90, 1.07). Among four investigated CRP genetic variants, only SNP rs1205 was significantly associated with CRC-specific (comparing the CT and CC genotypes with TT genotype, HR 0.54, 95% CI 0.35, 0.83 and HR 0.58, 95% CI 0.38, 0.88, respectively) and all-cause mortality (HR 0.58, 95% CI 0.40, 0.85 and 0.64, 95% CI 0.44, 0.92, respectively).

Conclusions

The results of this prospective cohort study do not support a role of pre-diagnostic CRP concentrations on mortality in individuals with CRC. The observed associations with rs1205 deserve further scientific attention.
Long anterior lens zonules with retinal stripes: a case report
Authors: Cao Xiaolu , Qin Jiayin , Li Zhiyong , Jia Peipei , Gao Beibei , Feng Lin , Wang Wei
Published: June 2022

Background

Long anterior lens zonules   (LAZs) is a rare disease that was mostly conducted among African Americans. Through the observation of a Chinese patient, we discoverd that the disease may show different characteristics in Asians.

Case presentation

A patient with vision loss due to a macular hole was found to have several special clinical signs during vitrectomy combined with phacoemulsification and intraocular lens implantation surgery in our hospital, including radially oriented lines on the anterior capsule with pigment, a shallow anterior chamber, slightly high intraocular pressure, and radial retinal stripes in the peripheral retina. Finally, he was diagnosed with long anterior lens zonule syndrome.

Conclusion

Clinicians need to pay more attention to the rare disease LAZs. It is important to tear the appropriate size of the anterior capsule so as to avoid radial capsular tearing and intraocular lens dislocation.
Development and validation of the ND10 to measure neck-related functional disability
Authors: MacDermid Joy C. , Walton David M.
Published: June 2022

Background

Previous neck-specific patient-reported outcome measures (PROMs) have tended to measure both symptoms and disability. This multi-staged study developed and evaluated a neck-specific PROM focusing on functional disability.

Methods

This study integrated findings from systematic reviews on neck-specific outcome measures, patient interviews, qualitative studies on neck disability, and iterative item testing to develop a 10-item measure of neck-related disability (ND10). Content validity was assessed by classifying items using the International Classification of Functioning, Disability and Health (ICF) and perspective linking. Patients (n = 78) with neck pain completed cognitive interviews, exploring items of the Neck Disability Index (NDI) and ND10, and completed structured questions related to literacy and relevance. Test–retest reliability and internal consistency were evaluated using intraclass correlation coefficients, Bland Altman graphs, and Cronbach’s alpha. Concurrent convergent validity was evaluated by comparing the ND10 to the NDI, Single Assessment Numeric Evaluation (SANE), and Disabilities of the Arm, Shoulder and Hand (DASH). Known group validity was determined by comparing ND10 scores from patients, who rated their neck as more or less than 1/2 of “normal” on the SANE, using t-tests.

Results

The ND10 requires respondents to make rational judgements about their neck-related body function and disability. It has high internal consistency (0.94) and re-test reliability (0.87; SEM = 3.2/100; MDC = 7.5); and no re-test bias (mean re-test difference of 0.6). It followed expected correlation patterns, being highly correlated with related multi-item PROMs (r = 0.85–0.91), and moderately correlated to the single-item SANE. More patients agreed that the ND10 was easily readable than did so for the NDI (84% vs 68%; p < 0.05). All the PROMs distinguished the patients who perceived themselves as being abnormal/normal defined by a dichotomized SANE (p < 0.01).

Conclusion

The ND10 is reliable and valid for measuring neck-related functional disability. Longitudinal and cross-cultural translation studies are needed to support future use.
Providing palliative care for residents in LTC facilities: an analysis of routine data of LTC facilities in Lower Saxony, Germany
Authors: Walther Wenke , Müller-Mundt Gabriele , Wiese Birgitt , Schneider Nils , Stiel Stephanie
Published: June 2022

Background

Demographic trends show an increasing number of elderly people and thus a growing need for palliative care (PC). Such care is increasingly being provided by long-term care (LTC) facilities. The present study aimed at exploring PC indicators of residents at LTC facilities belonging to a non-profit provider in Lower Saxony, Germany, in order to identify potential improvements.

Methods

A descriptive cross-sectional study was conducted, drawing on routine nursing chart data. Structural data from 16 participating LTC facilities and the care data of all residents who died in 2019 (N = 471) were collected anonymously between March and May 2020. Based on key literature on quality indicators of PC in LTC facilities in Germany, a structured survey was developed by a multidisciplinary research team. The descriptive, comparative and inferential data analysis was conducted using the SPSS software package.

Results

In total, the complete records of 363 (77%) residents who died in the participating LTC facilities in 2019 were retrieved. The records reflected that 45% of the residents had been hospitalized at least once during the last 6 months of their lives, and 19% had died in hospital. Advance care planning (ACP) consultation was offered to 168 (46%) residents, and 64 (38%) declined this offer. A written advance directive was available for 47% of the residents. A specialized PC team and hospice service volunteers were involved in caring for 6% and 14% of the residents, respectively. Cancer patients received support from external services significantly more frequently (p < .001) than did non-cancer patients. Differences emerged in the distribution of PC indicators between LTC facilities. Facilities that have more PC trained staff offered more ACP, supported by more specialized PC teams and hospice services, and had fewer hospitalizations. In addition, more volunteer hospice services were offered in urban facilities.

Conclusions

Overall, a rather positive picture of PC in participating LTC facilities in Germany emerged, although there were differences in the expression of certain indicators between facilities. ACP consultation, volunteer hospice services, and hospital admissions appeared to be superior in LTC facilities with more trained PC staff. Therefore, PC training for staff should be further promoted.
Components of case management in caring for patients with dementia: a mixed-methods study
Authors: Jerez-Barranco Desirée , Gutiérrez-Rodríguez Laura , Morilla-Herrera Juan Carlos , Cuevas Fernandez-Gallego Magdalena , Rojano-Perez Remedios , Camuñez-Gomez María Dolores , Sanchez-Del Campo José Luis , García-Mayor Silvia
Published: June 2022

Background

Case management has shown improvements in some health outcomes for dementia patients and their families. However, despite its benefits the components of case management in order to provide effective patient and family care remain unknown at present. Thus, the aim of this study is to identify the specific components of case management in caring for patients with dementia and to determine the necessary intensity of its deployment to enhance outcomes for these patients and their caregivers.

Methods

Mixed-methods study with a qualitative phase to characterise forms of service provision, according to the case management components involved, followed by a quantitative phase to analyse the correlations between different patterns of service provision, adverse events in patients and caregiver overload. This study will be based on the variables described in the RANGE.COM register.

Discussion

This research is expected to achieve a reproducible, evaluable set of interventions that can be modelled to optimise case management effectiveness for patients with dementia. Interactions between patients with dementia, their family caregivers and case management healthcare services, the components of these interactions and their association with the conditions of the individuals concerned are issues of great interest in the field of case management, which is constantly evolving.
Identification of novel proteins for lacunar stroke by integrating genome-wide association data and human brain proteomes
Authors: Zhang Chengcheng , Qin Fengqin , Li Xiaojing , Du Xiangdong , Li Tao
Published: June 2022

Background

Previous genome-wide association studies (GWAS) have identified numerous risk genes for lacunar stroke, but it is challenging to decipher how they confer risk for the disease. We employed an integrative analytical pipeline to efficiently transform genetic associations to identify novel proteins for lacunar stroke.

Methods

We systematically integrated lacunar stroke genome-wide association study (GWAS) (N=7338) with human brain proteomes (N=376) to perform proteome-wide association studies (PWAS), Mendelian randomization (MR), and Bayesian colocalization. We also used an independent human brain proteomic dataset (N=152) to annotate the new genes.

Results

We found that the protein abundance of seven genes (ICA1L,CAND2,ALDH2,MADD,MRVI1,CSPG4, andPTPN11) in the brain was associated with lacunar stroke. These seven genes were mainly expressed on the surface of glutamatergic neurons, GABAergic neurons, and astrocytes. Three genes (ICA1L,CAND2,ALDH2) were causal in lacunar stroke (P< 0.05/proteins identified for PWAS; posterior probability of hypothesis 4 ≥ 75 % for Bayesian colocalization), and they were linked with lacunar stroke in confirmatory PWAS and independent MR. We also found thatICA1Lis related to lacunar stroke at the brain transcriptome level.

Conclusions

Our present proteomic findings have identifiedICA1L,CAND2, andALDH2as compelling genes that may give key hints for future functional research and possible therapeutic targets for lacunar stroke.
An experimental model to induce digital dermatitis in beef calves
Authors: Thomas Anice D. , Pajor Edmond A. , Caddey Benjamin , Goldhawk Christy , Martins Larissa , Orsel Karin
Published: June 2022

Background

Digital dermatitis (DD) is a multifactorial infectious disease affecting the skin on feet of cattle causing erosion and inflammation above the heel bulbs. Some cases of DD cause lameness and significantly impact animal welfare and productivity. While DD has emerged as a concern for the beef industry, key information regarding early detection and its impact on cattle behaviour is lacking. The primary objective of this study was to determine if an established DD experimental model for dairy calves could be used to induce DD lesions in beef calves. A secondary objective was to describe changes in behaviour and pain associated with induction of DD lesions. Eight beef calves acquired from a single cow-calf operator were enrolled in the study. Upon enrolment, calves were evaluated and determined to be free of foot lesions. Within the experimental environment, calves were housed in individual pens and assigned to two groups (mock-inoculated and inoculated). Both hind feet of each calf were enrolled. Within calf, inoculation protocol was consistent, and a 28-day experimental protocol was employed. Two days prior to inoculation, both hind feet of each calf were abraded (area above the heel bulbs and below the dewclaws), moistened, and wrapped to facilitate an anaerobic condition. Feet were inoculated with macerated DD lesion material or mock inoculum and remained wrapped until clinical signs of DD or protocol endpoint.

Results

After a period of 14 to 18 days post inoculation, three of five inoculated calves developed clinical signs (lameness), and upon close inspection, DD lesions were present on at least one hind foot. Two of five inoculated calves did not develop lesions within 28 days. Zero of three mock-inoculated calves developed DD.Treponemaspp. were detected by quantitative polymerase chain reaction from biopsies of induced lesions. Measurements of behaviour prior to disease induction were numerically different between DD affected and mock-inoculated calves.

Conclusions

An experimental infection model established for dairy cattle was used to successfully induce acute DD lesions in three of five inoculated beef calves. This model can provide a framework to study intervention protocols and to evaluate the impact of DD on behaviour and pain.
A lung adenocarcinoma patient with co-mutations of MET and EGFR exon20 insertion responded to crizotinib
Authors: Chen Yan , Jiang Bo , He Yuange , Zhang Chu , Zhou Wenjie , Fang Cheng , Gu Dejian , Zhang Minxia , Ji Mei , Shi Juntao , Yang Xin
Published: June 2022

Background

Targeted therapy has revolutionized the treatment of patients with malignancies harboring mutations in driver genes and has brought a favorable survival benefit to the population with actionable oncogenic mutations. In recent years, theMETexon14 skipping mutation has been recognized as a potentially promising therapeutic target in non-small cell lung cancer (NSCLC). These changes are mutually exclusive with molecular drivers such asEGFR, KRAS, HER-2,BRAF, ALKandROS1. The prevalence rate of coexistingMETexon 14 mutations andEGFRsensitive mutations (L858R, exon 19 deletions) in Chinese population was reported to be 0.2% (3/1590). However, the coexistence ofMETexon 14 mutations withEGFRexon 20 insertion mutations has never been reported and the management of this subtype is not identified.

Case presentation

A 69-year-old male with a right lung adenocarcinoma (T4N2M0, IIIB) was confirmed to be positive forMETexon 14 skipping (c.3028_3028+1delGGinsTT, 44.4%),METamplification (copy number 4.4), andEGFRexon 20 insertion (p. N771_H773dup, 22.1%) mutations. After the progression of one cycle of chemotherapy (Pemetrexed 0.8 g d1), the patient was subsequently accepted treatment with Crizotinib (250 mg twice a day) and achieved an important clinical remission for six months until the development of brain metastases. Then, he was submitted to a cycle of anti-programmed cell death-1 (PD-1) therapy after failure of Crizotinib and eventually acquired resistance despite of the high expression of programmed death ligand-1 (PD-L1) and tumor mutational burden (TMB) status.

Conclusion

This case report provides treatment strategies for epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs)-untreated lung adenocarcinoma patients simultaneously carryingMETalterations andEGFRexon 20 insertion mutations. In addition, the signatures of PD-L1 or TMB expression were not the candidate for predicting the efficacy of immunotherapy in this context.
‘You say you are a TB doctor, but actually, you do not have any power’: health worker (de)motivation in the context of integrated, hospital-based tuberculosis care in eastern China
Authors: Zou Guanyang , McPake Barbara , Kielmann Karina
Published: June 2022

Background

In China, tuberculosis (TB) care, traditionally provided through the Centre for Disease Control (CDC), has been integrated into ‘designated’ public hospitals at County level, with hospital staff taking on delivery of TB services supported by CDC staff. Little is known about the impact of this initiative on the hospital-based health workers who were delegated to manage TB. Drawing on a case study of two TB ‘designated’ hospitals in Zhejiang province, we explored factors influencing hospital-based health workers’ motivation in the context of integrated TB service delivery.

Methods

We conducted 47 in-depth interviews with health officials, TB/hospital managers, clinicians, radiologists, laboratory staff and nurses involved in the integrated model of hospital-based TB care. Thematic analysis was used to develop and refine themes, code the data and assist in interpretation.

Results

Health workers tasked with TB care in ‘designated’ hospitals perceived their professional status to be low, related to their assessment of TB treatment as lacking need for professional skills, their limited opportunities for professional development, and the social stigma surrounding TB. In both sites, the integrated TB clinics were under-staffed: health workers providing TB care reported heavy workloads, and expressed dissatisfaction with a perceived gap in their salaries compared with other clinical staff. In both sites, health workers were concerned about poor infection control and weak risk management assessment systems.

Conclusions

Inadequate attention to workforce issues for TB control in China, specifically the professional status, welfare, and development as well as incentivization of infectious disease control workers has contributed to dissatisfaction and consequently poor motivation to serve TB patients within the integrated model of TB care. It is important to address the failure to motivate health workers and maximize public good-oriented TB service provision through improved government funding and attention to the professional welfare of health workers providing TB care in hospitals.
Exosome-mediated lncRNA SND1-IT1 from gastric cancer cells enhances malignant transformation of gastric mucosa cells via up-regulating SNAIL1
Authors: Jin Guohua , Zhang Jianguang , Cao Tingting , Chen Bang , Tian Yu , Shi Yang
Published: June 2022

Background

Gastric cancer (GC), as one of the most common malignancies across the globe, is the fourth leading cause of cancer-related deaths. Though a large body of research has been conducted to develop the therapeutic methods of GC, the survival rate of advanced patients is still poor. We aimed to dig into the potential regulatory mechanism of GC progression.

Methods

Bioinformatics tools and fundamental assays were performed at first to confirm the candidate genes in our study. The functional assays and mechanism experiments were conducted to verify the regulatory mechanisms of the genes underlying GC progression.

Results

Long non-coding RNA (lncRNA) SND1 intronic transcript 1 (SND1-IT1) is highly expressed in exosomes secreted by GC cells. SND1-IT1 was verified to bind to microRNA-1245b-5p (miR-1245b-5p) through competitive adsorption to promote ubiquitin specific protease 3 (USP3) messenger RNA (mRNA) expression. SND1-IT1 was validated to recruit DEAD-box helicase 54 (DDX54) to promote USP3 mRNA stability. SND1-IT1 induces malignant transformation of GES-1 cells through USP3. USP3 mediates the deubiquitination of snail family transcriptional repressor 1 (SNAIL1).

Conclusions

Exosome-mediated lncRNA SND1-IT1 from GC cells enhances malignant transformation of GES-1 cells via up-regulating SNAIL1.

Graphical Abstract
Fertility and contraception among women of reproductive age following a disaster: a scoping review
Authors: Strid Penelope , Snead Margaret Christine , Galang Romeo R. , Bish Connie L. , Ellington Sascha R.
Published: June 2022

Background

The prevalence and severity of disasters triggered by natural hazards has increased over the last 20 years. Women of reproductive age may encounter unique reproductive health challenges following a disaster. In this scoping review we identify gaps in literature to inform future research and search for potential associations between disasters by natural hazards and post-disaster fertility and contraception among women of reproductive age.

Methods

Medline (OVID), Embase (OVID), PsycInfo (OVID), CINAHL (Ebsco), Scopus, Environmental Science Collection (ProQuest Central), and Sociological Abstracts (ProQuest Central) were searched for articles published from 1980 through March 3, 2022 in English or Spanish language. Search terms were related to fertility, contraception, and disasters. We included original research that described a discrete natural hazard exposure, a population of women of reproductive age (15–49 years), and outcomes of fertility or contraception use or access, with pre- and post-disaster measures.

Results

Among 9788 citations, after initial exclusion 5121 remained for title and abstract review. One hundred and eighteen citations underwent full-text review and 26 articles met the inclusion criteria. Following critical appraisal, 20 articles were included in this review. Eighteen articles described outcomes related to fertility, five articles described contraception access, and three articles described contraception use.

Conclusions

Clearly defined exposure measures, robust analyses, and methodical post-disaster assessment periods, may address the current gaps within disaster research on fertility and contraception among women of reproductive age. Consistent patterns in fertility following a disaster triggered by natural hazards were not identified between or within disaster types. Studies that assessed contraception found no change in use, while some studies found a decrease in contraceptive access overall.
Aryl hydrocarbon receptor activation-mediated vascular toxicity of ambient fine particulate matter: contribution of polycyclic aromatic hydrocarbons and osteopontin as a biomarker
Authors: Ho Chia-Chi , Wu Wei-Te , Lin Yi-Jun , Weng Chen-Yi , Tsai Ming-Hsien , Tsai Hui-Ti , Chen Yu-Cheng , Yet Shaw-Fang , Lin Pinpin
Published: June 2022

Background

Exposure to ambient fine particulate matter (PM2.5) is associated with vascular diseases. Polycyclic aromatic hydrocarbons (PAHs) in PM2.5 are highly hazardous; however, the contribution of PM2.5-bound PAHs to PM2.5-associated vascular diseases remains unclear. The ToxCast high-throughput in vitro screening database indicates that some PM2.5-bound PAHs activate the aryl hydrocarbon receptor (AhR). The present study investigated whether the AhR pathway is involved in the mechanism of PM2.5-induced vascular toxicity, identified the PAH in PM2.5 that was the major contributor of AhR activation, and identified a biomarker for vascular toxicity of PM2.5-bound PAHs.

Results

Treatment of vascular smooth muscle cells (VMSCs) with an AhR antagonist inhibited the PM2.5-induced increase in the cell migration ability; NF-κB activity; and expression of cytochrome P450 1A1 (CYP1A1), 1B1 (CYP1B1), interleukin-6 (IL-6), and osteopontin (OPN). Most PM2.5-bound PAHs were extracted into the organic fraction, which drastically enhanced VSMC migration and increased mRNA levels of CYP1A1, CYP1B1, IL-6, and OPN. However, the inorganic fraction of PM2.5 moderately enhanced VSMC migration and only increased IL-6 mRNA levels. PM2.5 increased IL-6 secretion through NF-κB activation; however, PM2.5 and its organic extract increased OPN secretion in a CYP1B1-dependent manner. Inhibiting CYP1B1 activity and silencing OPN expression prevented the increase in VSMC migration ability caused by PM2.5 and its organic extract. The AhR activation potencies of seven PM2.5-bound PAHs, reported in the ToxCast database, were strongly correlated with their capabilities of enhancing the migration ability of VSMCs. Benzo(k)fluoranthene (BkF) contributed the most to the AhR agonistic activity of ambient PM2.5-bound PAHs. The association between PM2.5-induced vascular toxicity, AhR activity, and OPN secretion was further verified in mice; PM2.5-induced intimal hyperplasia in pulmonary small arteries and OPN secretion were alleviated in mice with low AhR affinity. Finally, urinary concentrations of 1-hydroxypyrene, a major PAH metabolite, were positively correlated with plasma OPN levels in healthy humans.

Conclusions

The present study offers in vitro, animal, and human evidences supporting the importance of AhR activation for PM2.5-induced vascular toxicities and that BkF was the major contributor of AhR activation. OPN is an AhR-dependent biomarker of PM2.5-induced vascular toxicity. The AhR activation potency may be applied in the risk assessment of vascular toxicity in PAH mixtures.
Comprehensive benchmarking of CITE-seq versus DOGMA-seq single cell multimodal omics
Authors: Xu Zhongli , Heidrich-O’Hare Elisa , Chen Wei , Duerr Richard H.
Published: June 2022

The recently developed method TEA-seq and similar DOGMA-seq single cell trimodal omics assays provide unprecedented opportunities for understanding cell biology, but independent evaluation is lacking. We explore the utility of DOGMA-seq compared to the bimodal CITE-seq assay in activated and stimulated human peripheral blood T cells. We find that single cell trimodal omics measurements after digitonin (DIG) permeabilization were generally better than after an alternative “low-loss lysis” (LLL) permeabilization condition. Next, we find that DOGMA-seq with optimized DIG permeabilization and its ATAC library provides more information, although its mRNA and cell surface protein libraries have slightly inferior quality, compared to CITE-seq.
Molecular characterization and determination of the biochemical properties of cathepsin L of Trichinella spiralis
Authors: Liu Ruo Dan , Meng Xiang Yu , Li Chen Le , Long Shao Rong , Cui Jing , Wang Zhong Quan
Published: June 2022

Cathepsin L is an important cysteine protease, but its function inT. spiralisremains unclear. The aim of this research was to explore the biological characteristics ofT. spiraliscathepsin L (TsCatL) and its role inT. spiralis-host interactions. Bioinformatic analysis revealed the presence of the cysteine protease active site residues Gln, Cys, His and Asn in mature TsCatL, as well as specific motifs of cathepsin L similar to ERFNIN and GYLND in the prepeptide of TsCatL. Molecular docking of mature TsCatL and E64 revealed hydrophobic effects and hydrogen bonding interactions. Two domains of TsCatL (TsCatL2) were cloned and expressed, and recombinant TsCatL2 (rTsCatL2) was autocatalytically cleaved under acidic conditions to form mature TsCatL. TsCatL was transcribed and expressed in larvae and adults and located in the stichosome, gut and embryo. Enzyme kinetic tests showed that rTsCatL2 degraded the substrate Z-Phe-Arg-AMC under acidic conditions, which was inhibited by E64 and PMSF and enhanced by EDTA, L-cysteine and DTT. The kinetic parameters of rTsCatL2 were a Km value of 48.82 μM and Vmax of 374.4 nM/min at pH 4.5, 37 °C and 5 mM DTT. In addition, it was shown that rTsCatL2 degraded haemoglobin, serum albumin, immunoglobulins (mouse IgG, human IgG and IgM) and extracellular matrix components (fibronectin, collagen I and laminin). The proteolytic activity of rTsCatL2 was host specific and significantly inhibited by E64. rTsCatL2 possesses the natural activity of a sulfhydryl-containing cysteine protease, and TsCatL is an important digestive enzyme that seems to be important for the nutrient acquisition, immune evasion and invasion ofTrichinellain the host.
Clinical yarning with Aboriginal and/or Torres Strait Islander peoples—a systematic scoping review of its use and impacts
Authors: Burke Alexander W. , Welch Susan , Power Tamara , Lucas Cherie , Moles Rebekah J.
Published: June 2022

Objectives

To explore how clinical yarning has been utilised as a health intervention for Aboriginal and/or Torres Strait Islander peoples and if there are any reported impacts yarning might have on health outcomes.

Study design

Systematic scoping review of published literature.

Data sources

A one-word search term “yarning” was applied in Scopus, EMBASE, CINAHL, MEDLINE, International Pharmaceutical Abstracts, Australian Public Affairs Information Service-Health, and the Aboriginal and/or Torres Strait Islander Health Bibliography databases. Databases were searched from inception to May 20, 2020.

Study selection

Studies were included where clinical yarning had been used as a health intervention. Inclusion and exclusion criteria were developed and applied according to PRISMA systematic and scoping review reporting methods.

Data synthesis

A total of 375 manuscripts were found from the initial data search. After removal of duplicates and removal of manuscripts based on abstract review, a total of 61 studies underwent full-text review. Of these, only five met the inclusion criteria of utilising yarning as a clinical intervention. Four of these studies described consumer self-reported health outcomes, with only one study looking at improvements in objective physiological health outcomes.

Conclusions

Whilst clinical yarning may be a culturally appropriate intervention in healthcare, there are limited studies that have measured the impact of this intervention. Further research may be needed to ascertain the true benefits of this intervention.
Determinants of COVID-19 vaccine behaviour intentions among the youth in Kenya: a cross-sectional study
Authors: Osur Joachim O. , Chengo Rehema , Muinga Evelyne , Kemboi Jackline , Sidibe Myriam , Rarieya Maggie
Published: June 2022

Introduction

COVID-19 has become a public health concern globally with increased numbers of cases of the disease and deaths reported daily. The key strategy for the prevention of COVID-19 disease is to enhance mass COVID-19 vaccination. However, mass vaccination faces challenges of hesitation to acceptance of the vaccine in the community. The youth may not be among the vulnerable population to severe COVID-19 disease but are highly susceptible to contracting the virus and spreading it. The aim of the study was to assess COVID-19 vaccine youth behavior intentions and their determinants in Kenya.

Methods

The study used a mixed method design, employing a cross-sectional survey and focused group discussions across 47 counties in Urban, Peri-Urban and Rural settings of Kenya. The interviewees were youths aged 18–35, registered in online platforms/peer groups that included Shujaaz, Brck Moja, Aiffluence, Y Act and Heroes for Change. Quantitative data was collected using Google forms. A total of 665 interviews were conducted. Quantitative data was analysed using STATA version 16. In this paper we report quantitative study findings.

Results

The findings of the study indicated that only 42% of the youth were ready to be vaccinated, with 52% adopting a wait and see approach to what happens to those who had received the vaccine and 6% totally unwilling to be vaccinated. The determinants of these behavior intentions included: the perceived adverse effects of the vaccine on health, inadequate information about the COVID-19 vaccine, conflicting information about COVID-19 vaccine from the social media, religious implications of the vaccine, impact of education level on understanding of the vaccine, perceived risk of contracting the COVID-19 disease, efficacy of the COVID-19 vaccine, COVID-19 affecting women than men and trust in the ministry of health to lead COVID-19 interventions. Significantly it was found that hesitancy is higher among females, protestants and those with post-secondary education. Lack of information and concerns around vaccine safety and effectiveness were main cause of COVID-19 vaccine hesitancy. Social media was the major source of information contributing to hesitancy. Other contributors to hesitancy included low trust in the MoH and belief that mass vaccination is not helpful.

Conclusion

Vaccine hesitancy remains high among the youth but the causes of it are modifiable and health systems need to have evidence based engagements with the youth to reduce vaccine hesitancy.