bluuebunny/crossref_metadata_2025 huggingface dataset:
‘Offending doesn't happen in a vacuum’: The backgrounds and experiences of children under the age of 14 years who offend
Authors: Reil Jerome , Lambie Ian , Allen Ruth
Published: March 2022

Relative to those who first offend in adolescence, younger children who offend are at increased risk of engaging in serious, persistent, and violent offending. In addition, these children are at risk of a range of adverse psychosocial outcomes across the lifespan. Early intervention with children at risk of offending is therefore critical to support children to thrive and reduce offending and victimisation rates. This study sought to explore the backgrounds and experiences of children who offend prior to the age of 14 years to shed light on the development of child offending and assist early intervention efforts. Interviews with family members (with lived experience of interacting with the child welfare and child offending system) and frontline child welfare and judicial professionals (who directly engage with children who offend) ( n = 33) were conducted. Their experiences show that children who offend have clear, significant, and unaddressed child welfare concerns, including growing up in poverty and experiencing abuse, which cumulatively impacts on children's normative development and can eventually culminate in offending. Participants called for urgent action to address the sociostructural concerns that underlie child welfare concerns and provide prompt and effective assistance to families in need to support children to thrive and prevent future victimisation.
Validation of a computational phenotype for finding patients eligible for genetic testing for pathogenic PTEN variants across three centers
Authors: Kothari Cartik , Srivastava Siddharth , Kousa Youssef , Izem Rima , Gierdalski Marcin , Kim Dongkyu , Good Amy , Dies Kira A. , Geisel Gregory , Morizono Hiroki , Gallo Vittorio , Pomeroy Scott L. , Garden Gwenn A. , Guay-Woodford Lisa , Sahin Mustafa , Avillach Paul
Published: March 2022

Background

Computational phenotypes are most often combinations of patient billing codes that are highly predictive of disease using electronic health records (EHR). In the case of rare diseases that can only be diagnosed by genetic testing, computational phenotypes identify patient cohorts for genetic testing and possible diagnosis. This article details the validation of a computational phenotype for PTEN hamartoma tumor syndrome (PHTS) against the EHR of patients at three collaborating clinical research centers: Boston Children's Hospital, Children's National Hospital, and the University of Washington.

Methods

A combination of billing codes from the International Classification of Diseases versions 9 and 10 (ICD-9 and ICD-10) for diagnostic criteria postulated by a research team at Cleveland Clinic was used to identify patient cohorts for genetic testing from the clinical data warehouses at the three research centers. Subsequently, the EHR—including billing codes, clinical notes, and genetic reports—of these patients were reviewed by clinical experts to identify patients with PHTS.

Results

The PTEN genetic testing yield of the computational phenotype, the number of patients who needed to be genetically tested for incidence of pathogenic PTEN gene variants, ranged from 82 to 94% at the three centers.

Conclusions

Computational phenotypes have the potential to enable the timely and accurate diagnosis of rare genetic diseases such as PHTS by identifying patient cohorts for genetic sequencing and testing.
Conducting clinical trials in persons with Down syndrome: summary from the NIH INCLUDE Down syndrome clinical trials readiness working group
Authors: Baumer Nicole T. , Becker Mara L. , Capone George T. , Egan Kathleen , Fortea Juan , Handen Benjamin L. , Head Elizabeth , Hendrix James E. , Litovsky Ruth Y. , Strydom Andre , Tapia Ignacio E. , Rafii Michael S.
Published: March 2022

The recent National Institute of Health (NIH) INCLUDE (INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE) initiative has bolstered capacity for the current increase in clinical trials involving individuals with Down syndrome (DS). This new NIH funding mechanism offers new opportunities to expand and develop novel approaches in engaging and effectively enrolling a broader representation of clinical trials participants addressing current medical issues faced by individuals with DS. To address this opportunity, the NIH assembled leading clinicians, scientists, and representatives of advocacy groups to review existing methods and to identify those areas where new approaches are needed to engage and prepare DS populations for participation in clinical trial research. This paper summarizes the results of the Clinical Trial Readiness Working Group that was part of the INCLUDE Project Workshop: Planning a Virtual Down Syndrome Cohort Across the Lifespan Workshop held virtually September 23 and 24, 2019.
Genomic sequencing of Thinopyrum elongatum chromosome arm 7EL, carrying fusarium head blight resistance, and characterization of its impact on the transcriptome of the introgressed line CS-7EL
Authors: Konkin David , Hsueh Ya-Chih , Kirzinger Morgan , Kubaláková Marie , Haldar Aparna , Balcerzak Margaret , Han Fangpu , Fedak George , Doležel Jaroslav , Sharpe Andrew , Ouellet Thérèse
Published: March 2022

Background

The tall wheatgrass speciesThinopyrum elongatumcarries a strong fusarium head blight (FHB) resistance locus located on the long arm of chromosome 7 (7EL) as well as resistance to leaf and stem rusts, all diseases with a significant impact on wheat production. Towards understanding the contribution ofTh. elongatum7EL to improvement of disease resistance in wheat, the genomic sequence of the 7EL fragment present in the wheat Chinese Spring (CS) telosomic addition line CS-7EL was determined and the contribution and impact of 7EL on the rachis transcriptome during FHB infection was compared between CS and CS-7EL.

Results

We assembled theTh. elongatum7EL chromosome arm using a reference-guided approach. Combining this assembly with the available reference sequence for CS hexaploid wheat provided a reliable reference for interrogating the transcriptomic differences in response to infection conferred by the 7EL fragment. Comparison of the transcriptomes of rachis tissues from CS and CS-7EL showed expression ofTh. elongatumtranscripts as well as modulation of wheat transcript expression profiles in the CS-7EL line. Expression profiles at 4 days after infection withFusarium graminearum,the causal agent of FHB, showed an increased in expression of genes associated with an effective defense response, in particular glucan endo-1,3-beta-glucosidases and chitinases, in the FHB-resistant line CS-7EL while there was a larger increase in differential expression for genes associated with the level of fungal infection in the FHB-susceptible line CS. One hundred and seven 7EL transcripts were expressed in the smallest 7EL region defined to carry FHB resistance.

Conclusion

7EL contributed to CS-7EL transcriptome by direct expression and through alteration of wheat transcript profiles. FHB resistance in CS-7EL was associated with transcriptome changes suggesting a more effective defense response. A list of candidate genes for the FHB resistance locus on 7EL has been established.
Gene loss, genome rearrangement, and accelerated substitution rates in plastid genome of Hypericum ascyron (Hypericaceae)
Authors: Claude Sivagami-Jean , Park Seongjun , Park SeonJoo
Published: March 2022

Background

Comparative genomic analysis exhibits dynamic evolution of plastid genome (plastome) in the clusioid clade of Malpighiales, which comprise five families, including multiple inversions and gene losses. Little is known about the plastome evolution in Hypericaceae, a large family in the clade. Only the plastome of one species, Cratoxylum cochinchinense, has been published.

Results

We generated a complete plastome sequence for Hypericum ascyron, providing the first complete plastome from the tribe Hypericeae (Hypericaceae). The H. ascyron plastome exhibits dynamic changes in gene and intron content, structure, and sequence divergence compared to the C. cochinchinense plastome from the tribe Cratoxyleae (Hypericaceae). Transcriptome data determined the evolutionary fate of the missing plastid genes infA, rps7, rps16, rpl23, and rpl32 in H. ascyron. Putative functional transfers of infA, rps7, and rpl32 were detected to the nucleus, whereas rps16 and rpl23 were substituted by nuclear-encoded homologs. The plastid rpl32 was integrated into the nuclear-encoded SODcp gene. Our findings suggested that the transferred rpl32 had undergone subfunctionalization by duplication rather than alternative splicing. The H. ascyron plastome rearrangements involved seven inversions, at least three inverted repeat (IR) boundary shifts, which generated gene relocations and duplications. Accelerated substitution rates of plastid genes were observed in the H. ascyron plastome compared with that of C. cochinchinense plastid genes. The higher substitution rates in the accD and clpP were correlated with structural change, including a large insertion of amino acids and losses of two introns, respectively. In addition, we found evidence of positive selection of the clpP, matK, and rps3 genes in the three branches related to H. ascyron. In particular, the matK gene was repeatedly under selection within the family Hypericaceae. Selective pressure in the H. ascyron matK gene was associated with the loss of trnK-UUU and relocation into the IR region.

Conclusions

The Hypericum ascyron plastome sequence provides valuable information for improving the understanding of plastome evolution among the clusioid of the Malpighiales. Evidence for intracellular gene transfer from the plastid to the nucleus was detected in the nuclear transcriptome, providing insight into the evolutionary fate of plastid genes in Hypericaceae.
Impact of renin–angiotensin–aldosterone system inhibition on mortality in critically ill COVID-19 patients with pre-existing hypertension: a prospective cohort study
Authors: Sato Kei , White Nicole , Fanning Jonathon P. , Obonyo Nchafatso , Yamashita Michael H. , Appadurai Vinesh , Ciullo Anna , May Meryta , Worku Elliott T. , Helms Leticia , Ohshimo Shinichiro , Juzar Dafsah A. , Suen Jacky Y. , Bassi Gianluigi Li , Fraser John F. , Arora Rakesh C. ,   COVID-19 Critical Care Consortium Investigators, Bassi Gianluigi Li , Suen Jacky Y. , Dalton Heidi J. , Laffey John , Brodie Daniel , Fan Eddy , Torres Antoni , Chiumello Davide , Elhazmi Alyaa , Hodgson Carol , Ichiba Shingo , Luna Carlos , Murthy Srinivas , Nichol Alistair , Ng Pauline Yeung , Ogino Mark , Marwali Eva , Yang Ian , Dip Grad , Grasselli Giacomo , Bartlett Robert , Burrell Aidan , Fraser John F.
Published: March 2022

Background

The influence of renin–angiotensin–aldosterone system (RAAS) inhibitors on the critically ill COVID-19 patients with pre-existing hypertension remains uncertain. This study examined the impact of previous use of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) on the critically ill COVID-19 patients.

Methods

Data from an international, prospective, observational cohort study involving 354 hospitals spanning 54 countries were included. A cohort of 737 COVID-19 patients with pre-existing hypertension admitted to intensive care units (ICUs) in 2020 were targeted. Multi-state survival analysis was performed to evaluate in-hospital mortality and hospital length of stay up to 90 days following ICU admission.

Results

A total of 737 patients were included—538 (73%) with pre-existing hypertension had received ACEi/ARBs before ICU admission, while 199 (27%) had not. Cox proportional hazards model showed that previous ACEi/ARB use was associated with a decreased hazard of in-hospital death (HR, 0.74, 95% CI 0.58–0.94). Sensitivity analysis adjusted for propensity scores showed similar results for hazards of death. The average length of hospital stay was longer in ACEi/ARB group with 21.2 days (95% CI 19.7–22.8 days) in ICU and 6.7 days (5.9–7.6 days) in general ward compared to non-ACEi/ARB group with 16.2 days (14.1–18.6 days) and 6.4 days (5.1–7.9 days), respectively. When analysed separately, results for ACEi or ARB patient groups were similar for both death and discharge.

Conclusions

In critically ill COVID-19 patients with comorbid hypertension, use of ACEi/ARBs prior to ICU admission was associated with a reduced risk of in-hospital mortality following adjustment for baseline characteristics although patients with ACEi/ARB showed longer length of hospital stay.

Clinical trial registration The registration number: ACTRN12620000421932; The date of registration: 30, March 2020; The URL of the registration: https://www.australianclinicaltrials.gov.au/anzctr/trial/ACTRN12620000421932.
Deep learning model can improve the diagnosis rate of endoscopic chronic atrophic gastritis: a prospective cohort study
Authors: Zhao Quchuan , Chi Tianyu
Published: March 2022

Background and aims

Chronic atrophic gastritis (CAG) is a precancerous form of gastric cancer. However, with pathological diagnosis as the gold standard, the sensitivity of endoscopic diagnosis of atrophy is only 42%. We developed a deep learning (DL)-based real-time video monitoring diagnostic model for endoscopic CAG and conducted a prospective cohort study to verify whether this diagnostic model could improve the diagnosis rate of endoscopic CAG compared with that of endoscopists.

Methods

A U-NET network was used to build a real-time video monitoring diagnostic model for endoscopic CAG based on DL. We enrolled 431 patients who underwent gastroscopy from October 1, 2020, to December 1, 2020. To keep the baseline data of enrolled patient uniform and control for confounding factors, we applied a paired design and included the same patients in both the DL and the endoscopist group.

Results

The DL model improved the diagnosis rate of endoscopic CAG compared with that of endoscopists. Compared with diagnoses by endoscopists, the proportions of moderate and severe CAG in the atrophy patients diagnosed by the DL model were significantly larger, the proportion of “type O” CAG was significantly larger, the number of atrophy sites found was significantly increased, and the number of biopsies was significantly decreased. Compared with diagnoses by endoscopists, in the atrophic lesions diagnosed by the DL model, the proportions of severe atrophy and severe intestinal metaplasia were significantly increased.

Conclusions

Our study suggested the DL model could improve the diagnosis rate of endoscopic CAG compared with that of endoscopists.

Trial registration: ChiCTR2100044458, 18/03/2020.
Kinematic analysis of activities of daily living performance in frail elderly
Authors: Schmidle Stephanie , Gulde Philipp , Herdegen Sophie , Böhme Georg-Eike , Hermsdörfer Joachim
Published: March 2022

Background

Frailty is accompanied by limitations of activities of daily living (ADL) and frequently associated with reduced quality of life, institutionalization, and higher health care costs. Despite the importance of ADL performance for the consequence of frailty, movement analyses based on kinematic markers during the performance of complex upper extremity-based manual ADL tasks in frail elderly is still pending.

The main objective of this study was to evaluate if ADL task performance of two different tasks in frail elderlies can be assessed by an activity measurement based on an acceleration sensor integrated into a smartwatch, and further to what degree kinematic parameters would be task independent.

Methods

ADL data was obtained from twenty-seven elderly participants (mean age 81.6 ± 7.0 years) who performed two ADL tasks. Acceleration data of the dominant hand was collected using a smartwatch. Participants were split up in three groups, F (frail,n = 6), P (pre-frail,n = 13) and R (robust,n = 8) according to a frailty screening. A variety of kinematic measures were calculated from the vector product reflecting activity, agility, smoothness, energy, and intensity.

Results

Measures of agility, smoothness, and intensity revealed significant differences between the groups (effect sizes combined over tasks η2p = 0.18 – 0.26). Smoothness was particularly affected by frailty in the tea making task, while activity, agility, a different smoothness parameter and two intensity measures were related to frailty in the gardening task. Four of nine parameters revealed good reliability over both tasks (r = 0.44 – 0.69). Multiple linear regression for the data combined across tasks showed that only the variability of the magnitude of acceleration peaks (agility) contributed to the prediction of the frailty score (R2 = 0.25).

Conclusion

The results demonstrate that ADL task performance can be assessed by smartwatch-based measures and further shows task-independent differences between the three levels of frailty. From the pattern of impaired and preserved performance parameters across the tested tasks, we concluded that in persons with frailty ADL performance was more impaired by physiological deficiencies, i.e., physical power and endurance, than by cognitive functioning or sensorimotor control.
Primary intra- and extradural extramedullary mesenchymal chondrosarcoma with isolated punctate calcification: case report and literature review
Authors: Chen Meigui , Lai Qingquan
Published: March 2022

Background

Mesenchymal chondrosarcoma (MCS) is an ultra-rare, high-grade subtype of chondrosarcoma affecting both bone and soft tissues. Extra-skeletal MCS rarely occurs in intra- and extradural regions.

Case presentation

We presented a case of intraspinal dumbbell-shaped MCS at the T12-L2 level with isolated punctate calcification in a 19-year-old male complaining of progressive lower back pain. Surgical treatment for removal of the tumor was performed. The postoperative pathological result confirmed MCS. The patient showed symptomatic improvement and follow-up MRI showed no evidence of recurrence or metastasis for nearly 1 year after surgery.

Conclusions

CT and MRI play an important role in differential diagnosis for intraspinal MCS. MCS should be added to the differential diagnosis of intraspinal dumbbell-shaped tumors, especially when radiological examinations reveal punctate calcification in a homogeneous enhanced tumor without dural tail sign. However, the final diagnosis depends on histopathological results. Despite the good prognosis of intraspinal MCS, close follow-up after operation is still necessary.
Understanding breast cancer risk factors: is there any mismatch between laywomen perceptions and expert opinions
Authors: Manouchehri E. , Taghipour A. , Ebadi A. , Homaei Shandiz F. , Latifnejad Roudsari R.
Published: March 2022

Background

Women’s perception and knowledge of breast cancer signs, symptoms, and risk factors could be conducive to breast cancer risk management and interventions. The present study aimed to explore Iranian laywomen perceptions and expert opinions regarding breast cancer risk factors.

Methods

This qualitative study was conducted from March to November 2019 in Mashhad, northeast of Iran. Through purposive sampling, 24 laywomen (women with and without BC) and 10 experts of different fields including oncology, surgery, gynecology and reproductive health were selected. Data collection was carried out using semi-structured interviews, which was mainly focused on the participants’ understanding and perception of BC risk factors. The data was analyzed utilizing conventional content analysis developed by Graneheim & Lundman. Components of trustworthiness, including credibility, dependability, confirmability, and transferability were considered.

Results

The main category of risk factors, which emerged from the lay participants’ data analysis, were “unhealthy lifestyle and habits” , “hormonal influences”, “environmental exposures”, “Individual susceptibility “and “belief in supernatural powers”. The experts had similar perspectives for certain risk factors, yet not for all. The category of “Individual history of disease” was emerged only from experts’ interviews.

Conclusion

In the present study, the lay participants’ perception concerning BC risk factors was found to be a mixture of cultural beliefs and the scientific knowledge dispersed by the media, internet, and health services. Primary prevention approaches, including awareness of breast cancer risk factors, are required for women to make improved health-related choices.
PARP inhibitors chemopotentiate and synergize with cisplatin to inhibit bladder cancer cell survival and tumor growth
Authors: Bhattacharjee Sayani , Sullivan Matthew J. , Wynn Rebecca R. , Demagall Alex , Hendrix Andrew S. , Sindhwani Puneet , Petros Firas G. , Nadiminty Nagalakshmi
Published: March 2022

Background

Management of bladder cancer (BLCA) has not changed significantly in the past few decades, with platinum agent chemotherapy being used in most cases. Chemotherapy reduces tumor recurrence after resection, but debilitating toxicities render a large percentage of patients ineligible. Recently approved immunotherapy can improve outcomes in only a third of metastatic BLCA patients. Therefore, more options for therapy are needed. In this study, we explored the efficacy of PARP inhibitors (PARPi) as single agents or as combinations with platinum therapy.

Methods

We treated BLCA cells with PARPi (olaparib, niraparib, rucaparib, veliparib, or talazoparib) alone or as the combination of cisplatin with PARPi. We then measured their survival, proliferation, apoptosis, as well as their ability to form colonies. BLCA xenografts in male SCID mice were treated similarly, followed by the assessment of their growth, proliferation, and apoptosis.

Results

PARPi niraparib and talazoparib were effective in reducing BLCA cell survival as single agents. Combinations of Cisplatin with talazoparib and niraparib effectively reduced the survival of BLCA cells, while veliparib was not effective even at high concentrations. In vivo, the combinations of cisplatin with niraparib, rucaparib, or talazoparib reduced BLCA xenograft growth significantly.

Conclusions

We provide evidence that PARPi can be effective against BLCA as single agents or as combinatorial therapy with cisplatin.
Associations between starting and stopping volunteering and physical activity among older adults - longitudinal evidence from the German Ageing Survey
Authors: Baumbach Linda , König Hans-Helmut , Hajek André
Published: March 2022

Background

Physical activity (PA) contributes to healthy aging. Several studies have investigated factors influencing PA. However, population-based studies evaluating associations between volunteering and changes in PA are lacking. Our aim was to clarify whether starting and stopping to volunteer is associated with changes in physical activity in older adults.

Method

We used data from the German Ageing Survey (wave 5 and 6 in the years 2014 and 2017), which is a representative survey of community-dwelling middle-aged and older adults. We included individuals ≥ 65 years (analytical sample: n = 5,682). PA was investigated using questions from the international physical activity questionnaire (IPAQ) and converted into metabolic equivalent of tasks (METs) per week. Changes in volunteering status in groups or organizations (yes/no) and their association with changes in PA were investigated in adjusted asymmetric fixed effects models stratified by sex.

Results

We found an association, between starting to volunteer and increased physical activity in older adults in the total sample (ß = 1,078.93, p = 0.052). This change reached significance for men (ß = 1,751.54, p = 0.016), but not for women (ß = 187.25, p = 0.832) in the stratified analyses. In the total sample, there was no association between stopping volunteering and decreases in PA (ß = -285.61, p = 0.543). This also held true in the stratified analyses for men (ß = -320.76, p = 0.583) and women (ß = -158.96, p = 0.845).

Conclusion

Our study identified an association between beginning to volunteer and increased physical activity among older men. Thus, beginning to volunteer may assist older men in increasing their physical activity levels.
Cross-country evidence on the role of national governance in boosting COVID-19 vaccination
Authors: Aida Takeshi , Shoji Masahiro
Published: March 2022

Background

Frequent mutations of the COVID-19 virus, such as the Delta and Omicron variants, have prolonged the pandemic. Rich countries have approved the booster shots (3rd doses) of vaccine, but this causes further delay of vaccination in developing countries. This raises the risk of further mutations, which may lower the efficacy of currently available vaccines. As herd immunity by universal vaccination is essential to end the pandemic, the COVID-19 Vaccine Global Access (COVAX) facility has been established to provide developing countries with subsidized vaccines. However, a critical issue is that the developing countries also need to effectively deploy vaccines to citizens. Although this argument suggests positive effects of good national governance on vaccination coverage, to the best of our knowledge, there is no cross-country evidence on the role of national governance in increasing the coverage of COVID-19 vaccines among citizens. The goal of this study was to examine the association between the national governance and vaccination coverage among developing countries.

Methods

Using cross-country data, an ordinary least squares regression was conducted to examine the association between the national governance index and three outcomes: (1) the number of days until the administration of the first dose in the country since December 2019, (2) the number of doses per 100 citizens as of the end of July 2021, and (3) the selection of approved vaccine manufacturers. The results were compared between the model including all countries and the model excluding the member countries of Organisation for Economic Co-operation and Development (OECD).

Results

A one standard deviation increase in the national governance index was associated with 9.1 days (95%CI: -15.76, -2.43) earlier administration of vaccines in the country, and a 12.1 dose increase (95%CI: 4.76, 19.34) per 100 citizens. These associations were larger in the non-OECD sample. The results also indicated the role of governance in the selection of the administered vaccines.

Conclusion

The provision of subsidized vaccines alone is not sufficient to control the spread of infection in developing countries; logistical and administrative support should also be offered, especially in countries with poor governance.

Trial registration

Not applicable
Risk factors for reoperation due to periprosthetic joint infection after elective total hip arthroplasty: a study of 35,056 patients using linked data of the Swedish Hip Arthroplasty Registry (SHAR) and Swedish Perioperative Registry (SPOR)
Authors: Qvistgaard Maria , Nåtman Jonatan , Lovebo Jenny , Almerud-Österberg Sofia , Rolfson Ola
Published: March 2022

Background

In Sweden, the incidence of a prosthetic joint infection (PJI) after a planned Total Hip Arthroplasty (THA) is 1.3%, but the worldwide incidence of PJI after THA is unknown. This study explores associations between reoperation due to PJI and potential risk factors.

Methods

Primary elective THA surgery registered in both the Swedish Hip Arthroplasty Registry (SHAR) and the Swedish Perioperative Registry (SPOR) between 1 January 2015 and 31 December 2019 were included in this registry study, resulting in a total study population of 35,056 cases. The outcome variable was reoperation as the result of PJI within a year after surgery. Data were analysed using a multivariable Cox regression model.

Results

Reoperation due to PJI occurred in 460 cases (i.e., 1.3% of the study population). Each year of age increased the risk with 2% (HR 1.02 Cl 1.01, 1.03 P = < 0.001). Compared to men, women had significantly less risk for reoperation (HR 2.17 Cl 1.79, 2.53 P = < 0.001). For patients with obesity (BMI > 30), the risk increased considerably compared to underweight, normal weight, or overweight patients (HR 1.89 Cl 1.43, 2.51 P = < 0.001). The risk also increased by 6% for every 10 min of operative time (HR 1.06 Cl 1.02, 1.09 P = < 0.001). Patients having general anaesthesia had greater risk compared to those with spinal anaesthesia (HR 1.34 Cl 1.04, 1.73 P = 0.024). Finally, a lateral approach showed higher risk of reoperation than a posterior approach (HR 1.43 Cl 1.18, 1.73 P = < 0.001).

Conclusion

Recognition of the several risk factors identified in this study will be important for the perioperative management of patients undergoing THA.
Primary duodenal papilla lymphoma producing obstructive jaundice: a case report
Authors: Wang Jicai , Han Jiantao , Xu Hanbing , Tai Sheng , Xie Xingwang
Published: March 2022

Background

Obstructive jaundice caused by primary duodenal lymphoma is a rare disease.

Case presentation

We reported a 59-year-old man who underwent endoscopic ultrasonography for obstructive jaundice and found a duodenal papilla tumor. Light microscopy revealed a non-Hodgkin's lymphoma. Immunohistochemical staining showed that the tumor was aggressive B-cell lymphoma. We carried out molecular targeted therapy combined with CHOP regimen chemotherapy.

Conclusion

Surgery plays an important role in resolving obstructive jaundice when accurate histological diagnosis cannot be made. After diagnosis, chemotherapy should play a central role in treatment.
A pilot study of endoscope-assisted MITLIF with fluoroscopy-guided technique: intraoperative objective and subjective evaluation of disc space preparation
Authors: Lin Guang-Xun , Chen Chien-Min , Rui Gang , Kim Jin-Sung
Published: March 2022

Background

Adequate discectomy and endplate preparation are extremely crucial steps for spinal interbody fusion. Minimally invasive transforaminal lumbar interbody fusion MITLIF technique is safe and effective. However, concerns exist regarding sufficient disc space preparation from unilateral access. The purpose of this study, was to demonstrate our preliminary experience in objective and subjective evaluation of disc space preparation intraoperatively during endoscope-assisted MITLIF with fluoroscopy-guided, describing some of its possible advantages, and analyzing its safety and feasibility.

Methods

From March 2018 to July 2019, three patients with degenerative spinal stenosis with radiculopathy and instability underwent endoscope-assisted MITLIF with fluoroscopy-guided. Patients’ demographic data, clinical parameters, subsidence, and fusion were collected.

Results

Patients were successfully treated by endoscope-assisted MITLIF with fluoroscopy-guided at single-level or two-level. Symptoms improved postoperatively in all patients, and no complications occurred during follow-up. No cage subsidence was observed. At 6-month postoperatively, there was bony fusion observed on computed tomography in two patients.

Conclusion

Endoscope-assisted MITLIF with fluoroscopy-guided is a safe and feasible technique to improve visualization during discectomy and endplate preparation objectively and subjectively, possibly increasing fusion rate and early time to fusion.
Polyphenols in Ilex latifolia Thunb. inhibit human lung cancer cell line A549 by regulation of the PI3K-Akt signaling pathway
Authors: Chen Jing , Du Yesheng , Long Yanyan , Tao Dan , Hu Mengyu , Jiang Yong , Wan Yue , Yang Dingyi
Published: March 2022

Background

The leaves of the plant Ilex latifolia Thunb. can be made into Kuding tea, which is a drink rich in polyphenols. This study aimed to observe the effect of Ilex latifolia Thunb. polyphenols (ILTPs) on human lung cancer cell line A549 (A549 cells) by regulating the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway.

Methods

In vitro cultured cells were treated with ILTPs; the proliferation of A549 cells and BEAS-2B human normal lung epithelial cells (Beas-2B cells) was observed using the 3-(4,5-dimethylazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and the survival status of A549 cells was observed by fluorescence staining. The expression of A549 cells was observed by quantitative polymerase chain reaction (qPCR) assay and Western blot analysis, while the compound composition of ILTPs was detected using high-performance liquid chromatography (HPLC).

Results

The experimental results showed that the proliferation of Beas-2B cells was unaffected by treatment with 0–500 μg/mL of ILTPs, whereas the decreased proliferation of A549 cells was observed with the increasing concentrations of ILTPs. Additionally, ILTPs elevated the levels of lactate dehydrogenase (LDH) and reactive oxygen species (ROS) and promoted apoptosis in A549 cells. The results of qPCR experiments showed that ILTPs upregulated caspase-9 mRNA expression and downregulated phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), mammalian target of rapamycin (mTOR), B-cell lymphoma-2 (Bcl-2), nuclear factor-κB (NF-κB), vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1 alpha (HIF-1α), and cyclooxygenase-2 (COX-2) expression in A549 cells. The Western blot analysis results also showed that ILTPs could reduce the protein expression of PI3K and Akt. The HPLC results showed that the main compounds present in the ILTPs were rutin, kaempferol, isochlorogenic acid A, isochlorogenic acid B, and isochlorogenic acid C.

Conclusions

Thus, this study indicated that the polyphenols of I. latifolia act as a class of natural functional food materials that potently suppress cancer by exerting their inhibitory effects on A549 cell proliferation through five key polyphenolic compounds.
Educational adaptation to clinical training during the COVID-19 pandemic: a process analysis
Authors: Dzara Kristina , Pusic Martin , Carlile Narath , Krupat Edward , Alexander Erik K.
Published: March 2022

Background

The COVID-19 pandemic is unprecedented in terms of the extent and rapidity of the disruption forced upon formal clinical education, most notably the extensive transition of clinical skills learning to interactive video-based clinical education.

Methods

In a phenomenologic study, we used thematic analysis to explore the COVID-19 disruption to clinical training and understand processes relating to adaptation in a large academic medical center. We conducted semi-structured interviews with 14 clinical teachers and 16 trainees representing all levels of clinical learning. Interviews occurred within the initial three months of the crisis, and data were analyzed following a thematic analysis coding process.

Results

We constructed eight themes synthesizing our participants’ perceptions of the immediate unanticipated disruption, noting in the process their alignment with a change management framework. These included: urgency in adapting, with an obvious imperative for change; overcoming inconsistent involvement and support through the formation of self-organized frontline coalitions; attempts to develop strategy and vision via initially reactive but eventually consistent communication; empowering a volunteer army through co-creation and a flattened hierarchy; and efforts to sustain improvement and positive momentum with celebration of trial, error, and growth. The majority of participants found positive outcomes resulting from the tumultuous change process. Moreover, they were now more readily accepting of change, and tolerant of the ambiguous and iterative nature inherent in the education change process. Many anticipated that some innovation would, or would at least deserve to, continue post- crisis.

Conclusions

The COVID-19 pandemic afforded an opportunity to study the content and process of change during an active crisis. In this case of clinical education, our findings provide insight into the ways an academic medical system adapts to unanticipated circumstances. We found alignment with broader organizational change management models and that, compared with crisis management models (and their shorter term focus on resolving such crises), stakeholders self-organized in a reliable manner that carries the potential advantage of preserving such beneficial change.
Ethical and regulatory implications of the COVID-19 pandemic for the medical devices industry and its representatives
Authors: Blakely Brette , Rogers Wendy , Johnson Jane , Grundy Quinn , Hutchison Katrina , Clay-Williams Robyn , Richards Bernadette , Maddern Guy
Published: March 2022

The development and deployment of medical devices, along with most areas of healthcare, has been significantly impacted by the COVID-19 pandemic. This has had variable ethical implications, two of which we will focus on here. First, medical device regulations have been rapidly amended to expedite approvals of devices ranging from face masks to ventilators. Although some regulators have issued cessation dates, there is inadequate discussion of triggers for exiting these crisis standards, and evidence that this may not be feasible. Given the relatively low evidence standards currently required for regulatory approval of devices, this further indefinite reduction in standards raises serious ethical issues. Second, the pandemic has disrupted the usual operations of device representatives in hospitals, providing an opportunity to examine and refine this potentially ethically problematic practice. In this paper we explain and critically analyse the ethical implications of these two pandemic-related impacts on medical devices and propose suggestions for their management. These include an endpoint for pandemic-related adjustments to device regulation or a mechanism for continued refinement over time, together with a review of device research conducted under crisis conditions, support for the removal and replacement of emergency approved devices, and a review of device representative credentialling.
Participatory development of CURA, a clinical ethics support instrument for palliative care
Authors: van Schaik Malene Vera , Pasman H.Roeline , Widdershoven Guy , Metselaar Suzanne
Published: March 2022

Background

Existing clinical ethics support (CES) instruments are considered useful. However, users report obstacles in using them in daily practice. Including end users and other stakeholders in developing CES instruments might help to overcome these limitations. This study describes the development process of a new ethics support instrument called CURA, a low-threshold four-step instrument focused on nurses and nurse assistants working in palliative care.

Method

We used aparticipatory developmentdesign. We worked together with stakeholders in a Community of Practice throughout the study. Potential end users (nurses and nurse assistants in palliative care) used CURA in several pilots and provided us with feedback which we used to improve CURA.

Results

We distinguished three phases in the development process.Phase one,Identifying Needs, focused on identifying stakeholder and end user needs and preferences, learning from existing CES instruments, their development and evaluation, and identify gaps.Phase two,Development, focused on designing, developing, refining and tailoring the instrument on the basis of iterative co-creation.Phase three,Dissemination, focused on implementation and dissemination. The instrument, CURA, is a four-step low-threshold instrument that fosters ethical reflection.

Conclusions

Participatory development is a valuable approach for developing clinical ethics support instruments. Collaborating with end users and other stakeholders in our development study has helped to meet the needs and preferences of end users, to come up with strategies to refine the instrument in order to enhance its feasibility, and to overcome reported limitations of existing clinical ethics instruments.
An exploration of young people’s, parent/carers’, and professionals’ experiences of a voluntary sector organisation operating a Youth Information, Advice, and Counselling (YIAC) model in a disadvantaged area
Authors: Hassan Shaima M. , Worsley Joanne , Nolan Lisa , Fearon Nicky , Ring Adele , Shelton Jane , McEgan David , Yameen Farheen , Khedmati Esmaeil Morasae , Kullu Cecil
Published: March 2022

Background

The present evaluation explored young people’s, parents/carers, and healthcare professionals’ perceptions of the Youth Information, Advice and Counselling (YIAC) model operated by a voluntary sector organisation in North West England. With an aim to understand the key components that contribute to enhancing the success of the YIAC model.

Method

Semi-structured interviews and focus groups with young people, parents/carers, and healthcare professionals were conducted. Data were analysed using thematic analysis.

Results

Five main themes were identified from the data: 1) Accessibility and flexibility; 2) Non-clinical model and environment; 3) Staff; 4) Partnership working; and 5) Promotion of positive mental health and wellbeing.

Conclusion

Findings highlight the importance of non-clinical, community-based, ‘one-stop-shop’ hubs for young people in disadvantaged areas. The key components highlighted as facilitating access and engagement include: opportunity to self-refer, choice of location, timely provision of support, non-clinical environment, age appropriate services, a non-hierarchical workforce, inclusive support for family and carers, a focus on wider, often social, issues, and collaboration with partner organisations. These findings suggest that early support hubs for young people’s mental health should have consistent, long-term funding and should exist in every local area.
Association of SGLT2 inhibitors with cardiovascular, kidney, and safety outcomes among patients with diabetic kidney disease: a meta-analysis
Authors: Kaze Arnaud D. , Zhuo Min , Kim Seoyoung C. , Patorno Elisabetta , Paik Julie M.
Published: March 2022

Background

We conducted a systematic review and meta-analysis of the cardiovascular, kidney, and safety outcomes of sodium-glucose cotransporter 2 inhibitors (SGLT2i) among patients with diabetic kidney disease (DKD).

Methods

We searched electronic databases for major randomized placebo-controlled clinical trials published up to September 30, 2021 and reporting on cardiovascular and kidney outcomes of SGLT2i in patients with DKD. DKD was defined as chronic kidney disease in individuals with type 2 diabetes. Random-effects meta-analysis models were used to estimate pooled hazard ratios (HR) and 95% confidence intervals (CI) for clinical outcomes including major adverse cardiovascular events (MACE: myocardial infarction [MI], stroke, and cardiovascular death), kidney composite outcomes (a combination of worsening kidney function, end-stage kidney disease, or death from renal or cardiovascular causes), hospitalizations for heart failure (HHF), deaths and safety events (mycotic infections, diabetic ketoacidosis [DKA], volume depletion, amputations, fractures, urinary tract infections [UTI], acute kidney injury [AKI], and hyperkalemia).

Results

A total of 26,106 participants with DKD from 8 large-scale trials were included (median age: 65.2 years, 29.7–41.8% women, 53.2–93.2% White, median follow-up: 2.5 years). SGLT2i were associated with reduced risks of MACE (HR 0.83, 95% CI 0.75–0.93), kidney composite outcomes (HR 0.66, 95% CI 0.58–0.75), HHF (HR 0.62, 95% CI 0.55–0.71), cardiovascular death (HR 0.84, 95% CI 0.74–0.96), MI (HR 0.78, 95% CI 0.67–0.92), stroke (HR 0.76, 95% CI 0.59–0.97), and all-cause death (HR 0.86, 95% CI 0.77–0.96), with no significant heterogeneity detected. Similar results were observed among participants with reduced estimated glomerular filtration rate (eGFR: < 60 mL/min/1.73m2). The relative risks (95% CI) for adverse events were 3.89 (1.42–10.62) and 2.50 (1.32–4.72) for mycotic infections in men and women respectively, 3.54 (0.82–15.39) for DKA, and 1.29 (1.13–1.48) for volume depletion.

Conclusions

Among adults with DKD, SGLT2i were associated with reduced risks of MACE, kidney outcomes, HHF, and death. With a few exceptions of more clear safety signals, we found overall limited data on the associations between SGLT2i and safety outcomes. More research is needed on the safety profile of SGLT2i in this population.
Salutary effects of moderate but not high intensity aerobic exercise training on the frequency of peripheral T-cells associated with immunosenescence in older women at high risk of breast cancer: a randomized controlled trial
Authors: Niemiro Grace M , Coletta Adriana M , Agha Nadia H. , Mylabathula Preteesh Leo , Baker Forrest L. , Brewster Abenaa M , Bevers Therese B , Fuentes-Mattei Enrique , Basen-Engquist Karen , Katsanis Emmanuel , Gilchrist Susan C , Simpson Richard J.
Published: March 2022

Background

Immunosenescence is described as age-associated changes within the immune system that are responsible for decreased immunity and increased cancer risk. Physically active individuals have fewer ‘senescent’ and more naïve T-cells compared to their sedentary counterparts, but it is not known if exercise training can rejuvenate ‘older looking’ T-cell profiles. We determined the effects of 12-weeks supervised exercise training on the frequency of T-cell subtypes in peripheral blood and their relationships with circulating levels of the muscle-derived cytokines (i.e. ‘myokines’) IL-6, IL-7, IL-15 and osteonectin in older women at high risk of breast cancer. The intervention involved 3 sessions/week of either high intensity interval exercise (HIIT) or moderate intensity continuous exercise (MICT) and were compared to an untrained control (UC) group.

Results

HIIT decreased total granulocytes, CD4+ T-cells, CD4+ naïve T-cells, CD4+ recent thymic emigrants (RTE) and the CD4:CD8 ratio after training, whereas MICT increased total lymphocytes and CD8 effector memory (EM) T-cells. The change in total T-cells, CD4+ naïve T-cells, CD4+ central memory (CM) T-cells and CD4+ RTE was elevated after MICT compared to HIIT. Changes in $$ \dot{\mathrm{V}}{\mathrm{O}}_{2\max } $$

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after training, regardless of exercise prescription, was inversely related to the change in highly differentiated CD8+ EMRA T-cells and positively related to changes in β2-adrenergic receptor (β2-AR) expression on CM CD4+ and CM CD8+ T-cells. Plasma myokine levels did not change significantly among the groups after training, but individual changes in IL-7 were positively related to changes in the number of β2-AR expressing CD4 naïve T cells in both exercise groups but not controls. Further, CD4 T-cells and CD4 naive T-cells were negatively related to changes in IL-6 and osteonectin after HIIT but not MICT, whereas CD8 EMRA T-cells were inversely related to changes in IL-15 after MICT but not HIIT.

Conclusions

Aerobic exercise training alters the frequency of peripheral T-cells associated with immunosenescence in middle aged/older women at high risk of breast cancer, with HIIT (pro-senescent) and MICT (anti-senescent) evoking divergent effects. Identifying the underlying mechanisms and establishing whether exercise-induced changes in peripheral T-cell numbers can alter the risk of developing breast cancer warrants investigation.