bluuebunny/crossref_metadata_2025 huggingface dataset:
Growth, body composition and bone mineral density among pubertal male athletes: intra-individual 12-month changes and comparisons between soccer players and swimmers
Authors: Costa Daniela C. , Valente-dos-Santos João , Sousa-e-Silva Paulo , Martinho Diogo V. , Duarte João P. , Tavares Oscar M. , Castanheira Joaquim M. , Oliveira Tomás G. , Abreu Sandra , Leite Neiva , Agostinete Ricardo R. , Fernandes Rômulo A. , Courteix Daniel , Coelho-e-Silva Manuel J.
Published: May 2022

Background

Puberty is a period of intense changes in human body and, additionally, participation in sports is viewed as prominent form of physical activity among male adolescent athletes. The current study was aimed to examine the intra-individual changes in body composition and bone tissue during years of maximal growth and the effect of 12-month participation in sports contrasting in mechanical impact.

Methods

The sample included 40 male adolescent athletes (soccer: n = 20; swimming: n = 20) aged 12.57 ± 0.37 years who were followed for 12 months. Stature and body mass were measured, bone mineral content (BMC), areal bone mineral density (aBMD), lean soft and fat tissues assessed using DXA. Food intake was estimated using a questionnaires and training sessions individually monitored. Repeated measures ANOVA tested the differences between sports and 12-month intra-individual variation (time moments: TM1, TM2). The analyses on aBMD for total body and total body less head were repeated controlling for variation in stature at baseline.

Results

Soccer players completed 63 ± 31 sessions (95 ± 47 h). Respective values for swimmers were 248 ± 28 sessions and 390 ± 56 h. In general, the analysis of aBMD as dependent variable evidenced significant effect of sport-associated variation (F = 5.254, p < 0.01; η2 = 0.35) and 12-month increments, particularly at lower limbs (F = 97.238, p < 0.01; η2 = 0.85). Respective mean values for aBMD were SCCTM1 = 0.885 g.cm−2, SWMTM1 = 0.847 g.cm−2, SCCTM2 = 0.939 g.cm−2, SWMTM2 = 0.880. Regarding the lean soft tissue, the magnitude of effects was very large for intra-individual variation (F = 223.043, p < 0.01; η2 = 0.92) and moderate between sports (F = 7.850, p < 0.01; η2 = 0.41): SCCTM1 = 30.6 kg, SWMTM1 = 34.9 kg, SCCTM2 = 35.8 kg, SWMTM2 = 40.5 kg). Finally, d-cohen values reporting percentage of intra-individual changes in aBMD between soccer players ad swimmers were large for the trochanter (d = 1.2; annual increments: SCC = 8.1%, SWM = 3.6%).

Conclusion

Puberty appeared as a period of significant intra-individual changes in lean soft tissue and bone mineral density. With increasing accumulated training experience, mean difference between sports contrasting in mechanical impact tended to me more pronounced in particular at the lower limbs.
Beaten but not down! Exploring resilience among female sex workers (FSWs) in Nairobi, Kenya
Authors: Wanjiru Rhoda , Nyariki Emily , Babu Hellen , Lwingi Ibrahim , Liku Jennifer , Jama Zaina , Kung’u Mary , Ngurukiri Polly ,   The Maisha Fiti Study Champions, Oside Daisy , Atieno Agnes , Watata Agnes , Gwala Demitila , Kamene Ruth , Akinyi Mary , Njau Faith , Nyamweya Chrispo , Shah Pooja , Okumu Monica , Weiss Helen , Kaul Rupert , Beattie Tara S. , Kimani Joshua , Seeley Janet
Published: May 2022

Background

In Kenya sex work is illegal and those engaged in the trade are stigmatized and marginalized.

We explored how female sex workers in Nairobi, Kenya, utilize different resources to navigate the negative consequences of the work they do.

Methods

Qualitative data were collected in October 2019 from 40 FSWs who were randomly sampled from 1003 women enrolled in the Maisha Fiti study, a 3-year longitudinal mixed-methods study exploring the relationship between HIV risk and violence and mental health. All interviews were audio-recorded, transcribed and translated. Data were thematically coded and analyzed using Nvivo 12.

Results

Participants’ age range was 18–45 years. Before entry into sex work, all but one had at least one child. Providing for the children was expressed as the main reason the women joined sex work. All the women grew up in adverse circumstances such as poor financial backgrounds and some reported sexual and physical abuse as children. They also continued to experience adversity in their adulthood including intimate partner violence as well as violence at the workplace. All the participants were noted to have utilised the resources they have to build resilience and cope with these adversities while remaining hopeful for the future. Motherhood was mentioned by most as the reason they have remained resilient. Coming together in groups and engaging with HIV prevention and treatment services were noted as important factors too in building resilience.

Conclusion

Despite the adverse experiences throughout the lives of FSWs, resilience was a key theme that emerged from this study. A holistic approach is needed in addressing the health needs of female sex workers. Encouraging FSWs to come together and advocating together for their needs is a key resource from which resilience and forbearance can grow. Upstream prevention through strengthening of education systems and supporting girls to stay in school and complete their secondary and/or tertiary education would help them gain training and skills, providing them with options for income generation during their adult lives.
Transumbilical single-site laparoscopic parallel mattress suturing prevents bleeding and chronic pelvic pain in myomectomy: a retrospective cohort study of 124 cases with intramural fibroids
Authors: Zeng Xi , Li Lin , Ye Hui , Xi Mingrong
Published: May 2022

Background

The most common complications of myomectomy are intraoperative hemorrhage and postoperative adhesion. The key point to overcome this problem is to improve suture quality. However, to date, there is still no consensus on the optimal method of uterine repair. In this study, we explored the effectiveness and feasibility of single-site laparoscopic parallel mattress sutures to reduce intraoperative bleeding and postoperative adhesion.

Methods

A retrospective cohort analysis was performed, according to the STROBE guidelines, on 124 patients with intramural fibroids admitted between May 2020 and April 2021. The cases were divided into two groups based on the description of the uterine incision suture in the surgical records, including 68 cases in the parallel mattress suture (PMS) group and 56 cases in the simple continuous suture (SCS) group. Operation-related indicators, bleeding indicators, surgical complications, scar reduction index 1 month after surgery, and the incidence of chronic pelvic pain 6 months after the surgery were observed. Independent sample t-tests and Mann–Whitney U tests were performed for the measurement data, and Pearson Chi-square tests were performed for count data. Statistical significance was set at P < 0.05.

Results

There was no significant difference in the baseline characteristics between the two groups. All operations were performed under transumbilical single-site laparoscopy without conversion. Compared to the SCS group, the PMS group had earlier postoperative anal exhaust (14.3 ± 6.7 h vs. 19.2 ± 9.6 h, P = 0.002), fewer postoperative hemoglobin drops (7.6 ± 3.7 g/L vs. 11.6 ± 4.3 g/L, P = 0.000), smaller uterine scars (3.7 ± 1.9 cm vs. 5.2 ± 1.8 cm, P = 0.000), and a larger uterine scar reduction index (50.2% vs. 31.0%, P = 0.000) one month after surgery and less chronic pelvic pain 6 months after surgery (2.9% vs. 12.5%, P = 0.016). No difference was found in auxiliary trocar usage, transfusion rate, operation time, hospital stay, or perioperative complications between the two groups.

Conclusion

Seromuscular parallel mattress sutures during myomectomy can prevent pinhole errhysis of the uterine incision, achieve complete serosal and aesthetic incisions, and reduce postoperative chronic pelvic pain. It is effective and feasible to complete a parallel mattress suture during myomectomy via single-site laparoscopy. Further prospective studies are required to determine its efficacy as well as pregnancy outcomes.
Dentist perceptions about the value of teledentistry
Authors: Tiwari Tamanna , Diep Vuong , Tranby Eric , Thakkar-Samtani Madhuli , Frantsve-Hawley Julie
Published: May 2022

Background

Teledentistry has expanded access to oral health care by allowing patients and providers the option to receive care using technology and telecommunications. This study used a cross-sectional, mixed-methods design to evaluate dentists’ perceptions in the United States and understanding of the value and scope of teledentistry in their practices and to adopt virtual encounters as a care delivery methodology.

Methods

This study used a cross-sectional, mixed-methods design. The DentaQuest Partnership for Oral Health Advancement (now CareQuest Institute for Oral Health) conducted an electronic survey of providers in the DentaQuest Network that assessed the impact of COVID-19 on dental practices' patient volume, staffing, dental insurance carriers, treatment protocols, and the office's pre-and post-COVID finances. A total of 2767 dental providers completed the survey with a response rate of 13%. Qualitative interviews were then conducted with ten providers to get more in-depth information on teledentistry. Descriptive statistics summarize the survey population. Thematic analysis, which allows both deductive and inductive approaches, were used to analyze the interviews.

Results

About 23% of the dentists used teledentistry or virtual platforms. Findings illustrate that early adopter dentists were more likely to perceive the benefits of teledentistry as being more significant than its drawbacks. Late/resistant adopters to teledentistry were less aware of its benefits and were more focused on the drawbacks, such as upfront cost. Late adopters were also concerned about the level of care delivered through teledentistry.

Conclusions

This study explored dentists’ perceptions of teledentistry. Expanding access to care was recognized as one of the greater values of teledentistry.
Novel insight into the correlation between hernia orifice of cystocele and lower urinary tract function: a pilot study
Authors: Kitta Takeya , Abe Hirokazu , Ting-wen Huang , Fujikawa Masahiro , Nakazono Minoru , Sasa Taiki , Doi Yukiko , Toki Sari , Okada Daigo , Ochi Atsuhiko , Suzuki Koichiro , Kitagawa Yasuhide , Shinohara Nobuo
Published: May 2022

Background

It has been hypothesized that women with significant pelvic organ prolapse (POP), particularly of the anterior vaginal wall, may have voiding dysfunction (VD). Although the VD mechanism due to cystocele is not fully understood, different vaginal compartments have rarely been closely examined. This study attempted to further elucidate the correlation between POP and VD through a new subgroup classification using cystoscopy.

Methods

This study reviewed clinical records of 49 women who underwent cystocele repair. All patients were scheduled for laparoscopic sacrocolpopexy, preoperatively underwent uroflowmetry and postvoid residual urine volume (PVR) measurement, and completed pelvic floor function questionnaires. Bladder examination by cystoscopy was additionally performed using the lithotomy position with the Valsalva maneuver.

Results

Subjects were divided into four groups according to hernia orifice presence determined by cystoscopy, which included the trigone type, posterior wall type, trigone and urethra type, and trigone and posterior wall type. The posterior wall type had statistically higher PVR values versus the trigone and posterior wall type (P = 0.013). The posterior wall type had statistically lower values for average urine flow rate versus the urethra and trigone type (P = 0.020). There were no significant differences noted in the pelvic floor function questionnaires among the four groups.

Conclusions

A new bladder defect classification based upon hernia orifice location was associated with lower urinary tract function. Posterior wall hernia presence caused significant voiding function deterioration. This new subgroup classification, which can more clearly identify and indicate bladder function, is also comparable among patients.
Malignant transformation of endometriosis in a laparoscopic trocar site a case report
Authors: Han Ling , Zhang Bingyi
Published: May 2022

Background

Malignant transformation of endometriosis is infrequent at the laparoscopic trocar site. Although malignant transformation is uncommon, it must be acknowledged in order to achieve radical resection.

Case presentation

We report on a 54-year-old woman with trocar site endometriosis 2 years after laparoscopic ovarian endometrial resection. Physical examination revealed a subcutaneous solid tumor with a diameter of 3 cm surrounding the scar of laparoscopic surgery in the right lower abdomen. Transabdominal ultrasonography showed a cystic tumor in the subcutaneous adipose layer of the right lower abdomen. The pathological diagnosis was poorly differentiated endometrioid carcinoma. Hysterectomy, bilateral salpingo-oophorectomy and pelvic lymphadenectomy were then performed. Histological examination revealed mixed endometrioid carcinoma and clear cell carcinoma. After six cycles of chemotherapy, computed tomography showed no signs of recurrence.

Conclusions

Malignant transformation of laparoscopic endometriosis is very uncommon, and the diagnosis and stage are determined by clinical manifestations and imaging examination. The main therapy methods are radical surgery combined with neoadjuvant chemotherapy and adjuvant radiotherapy. At the same time, reducing iatrogenic abdominal incision implantation is an effective prevention method.
"I expected little, although I learned a lot": perceived benefits of participating in HIV risk reduction sessions among women engaged in sex work in Uganda
Authors: Sensoy Bahar Ozge , Nabunya Proscovia , Nabayinda Josephine , Witte Susan S. , Kiyingi Joshua , Mayo-Wilson Larissa Jennings , Filippone Prema , Yang Lyla Sunyoung , Nakigudde Janet , Tozan Yesim , Ssewamala Fred M.
Published: May 2022

Background

The global HIV burden remains a public health concern. Women engaged in sex work (WESW) are at higher risk of acquiring HIV compared to the general adult population. Uganda reports high rates of HIV prevalence among WESW. While WESW in Uganda have long been the subject of surveillance studies, they have not been targeted by theory-informed HIV prevention intervention approaches. In this study, we explored the perceived benefits of an evidence-based HIV risk reduction intervention that was implemented as part of a combination intervention tested in a clinical trial in Uganda.

Methods

As part of a larger randomized clinical trial, we conducted semi-structured in-depth interviews with 20 WESW selected using a stratified purposive sampling. All interviews were conducted in Luganda, language spoken in the study area, and audio-recorded. They were transcribed verbatim and translated to English. Thematic analysis was used to analyze the data.

Results

WESW’s narratives focused on: (1) condom use; (2) alcohol/drug consumption; (3) PrEP use; (4) “handling” customers; and (5) "massaging” customers. WESW agreed that male condom was one of the important learning points for them and planned to continue using them while female condoms were received with mixed reactions. Many women appreciated receiving information about the risks of consuming alcohol and drugs, and discussed how they reduced/ eliminated their consumption. PrEP information was appreciated though identified by fewer WESW. Handling a client was discussed as a helpful strategy for safer sex through improved ability to convince customers to use condoms or avoiding sex. Massaging was also beneficial to avoid penetrative sex, but similar to female condom, massaging also yielded mixed perceptions.

Conclusion

WESW found the intervention beneficial and described ways in which it improved their ability to engage in safer sex and stay healthy. The fact that WESW identified other strategies beyond condom use as helpful underlines the importance of adopting a comprehensive approach to behavioral interventions targeting HIV prevention even when combined with other interventions. Additionally, WESW’s narratives suggest that incorporating the tenets of social cognitive theory and harm reduction approaches in HIV prevention among this population can result in risk behavior change.
Effects of an internationalization at home (IAH) programme on cultural awareness among medical and nursing students in Hong Kong and Indonesia during the COVID-19 pandemic: a mixed-methods study
Authors: Kor Patrick Pui Kin , Yu Clare Tsz Kiu , Triastuti Ida Ayu , Sigilipoe Mitra Andini , Kristiyanto Haryo Dimasto , Pratiwi Johana Puspasari Dwi , Perdamaian Teguh Kristian , Li Lisa Mengli , Pang Phyllis Chui Ping , Widagdo The Maria Meiwati
Published: May 2022

Background

The COVID-19 pandemic has severely impacted the learning experience of students by limiting their opportunities for face-to-face intercultural exchanges. Given the importance of cultural competence in medical education, there is a need to develop a programme that promotes cultural awareness, but that offers more flexibility in terms of outbound mobility. This study aims to evaluate the effectiveness of an internationalization at home programme and to explore the learning experiences of medical and nursing students from Hong Kong and Indonesia.

Methods

Students were recruited from two universities in Hong Kong and Indonesia. They attended an online internationalization at home programme designed by members of the research team from both countries. A mixed-methods study was conducted using a concurrent triangulation approach.

A pre-test post-test design was used to evaluate the effects of the programme on cultural awareness, and four focus groups were conducted to explore the students’ experiences in the programme. Quantitative and qualitative data were analysed by T-test and reflexive thematic analysis, respectively. Data were integrated and triangulated using joint displays by comparing findings from both sources.

Results

One hundred and forty-eight students from Hong Kong and Indonesia participated in the study. After the programme, there was a significant improvement in cultural awareness. Three themes were identified: (1) learning process: enjoyable, but a desire remains for face-to-face cross-cultural communication; (2) learning outcomes: gained cultural awareness, developed cultural sensitivity, had an opportunity to practice language and learn about new learning styles; (3) factors influencing learning outcomes: facilitators (micro-movie and active communication) and barriers (language barrier, inappropriate time arrangement, insufficient prior briefing).

Conclusion

This programme achieved the learning outcomes by successfully enhancing the cultural awareness of students during a time of pandemic when outbound student exchanges were not possible. Further adaptations of the programme are required to enhance different learning outcomes.
Pain assessment practice and associated factors among nurses working at adult care units in public hospitals in Wolaita Zone, Southern Ethiopia, 2021
Authors: Melile Mengesha Badeg , Moga Lencha Fikre , Ena Digesa Lankamo
Published: May 2022

Background

Using standard pain assessment techniques is a cornerstone for effective pain management. Pain is not assessed in a standardized manner in numerous practice settings. The problem of applying pain assessment principles was found to be higher in low-income countries. Very limited evidence indicates the standard of pain assessment practice among nurses in Ethiopia. Therefore, the purpose of this study was to identify pain assessment practice and associated factors among nurses working at adult care units in public hospitals in the Wolaita Zone, Southern Ethiopia.

Methods

A cross-sectional study was conducted among 290 nurses working at adult care units in public hospitals in Wolaita zone. Data were collected from February to March 2021. A structured self-administered questionnaire was used for data collection. Epi Data 4.6 was used to enter the data, and SPSS version 26 was used to analyze the data. A logistic regression model was used, and statistical significance was declared at P ≤ 0.05. An adjusted odds ratio with 95%CI was used to measure the degree of association.

Results

A total of 267 nurses participated in the study, giving a response rate of 97.8%. Almost three-fourths (73.8%) of the study nurses reported that they assessed pain for their patients. Only 23.6% of the study nurses discussed pain assessment scores during a nurse-to-nurse report. Below, half (47.2%) of the study participants documented pain assessment scores. The proportion of nurses with good pain assessment practice was found to be 38.2%.

The odds of having good pain assessment practice among nurses who received training on pain management was two times higher than its counterpart. The nurses who perceived organizational support were twice more likely to have good pain assessment practice than their counterparts.

Conclusion

Nurses’ pain assessment practice was found to be low. Moreover, a substantial proportion of the study nurses did not discuss pain assessment scores during a nurse-to-nurse report with low documentation practice. Continuous professional development through in-service training and education is crucial to the improvement of nurses’ pain assessment practice. Furthermore, ameliorating organizational support by means of a supportive working environment is suggested to the betterment of nurses’ assessment practice.
A cross-sectional survey of smoking and cessation support policies in a sample of homeless services in the United Kingdom
Authors: Cox Sharon , Murray Jaimi , Ford Allison , Holmes Lucy , Robson Deborah , Dawkins Lynne
Published: May 2022

Background

Smoking is extremely common amongst adults experiencing homelessness. To date, there is no nationally representative data on how tobacco dependence is treated and if and how smoking cessation is supported across the homeless sector. The aim of this study was to document smoking and e-cigarette policies of UK homeless services and identify areas of good practice and where improvements could be made.

Methods

A cross-sectional survey with homeless centre staff was conducted between June 2020-December 2020 totalling 99 homeless centres. Quotas were stratified based on population and service type across Scotland, Northern Ireland, Wales, and England. Interviews were conducted over the phone or online in a minority of cases. Survey questions were themed to assess, i) onsite smoking and e-cigarette (vaping) policies ii) screening and recording of smoking status, iii) cessation training and resources available to staff, iv) cessation support for service users.

Results

92% accounted for smoking within their policies in some form (stand-alone policy (56%) or embedded within another health and safety policy (36%)). 84% allowed smoking in at least some (indoor and outdoor) areas. In areas where smoking was not allowed, vaping was also disallowed in 96% of cases. Staff smoking rates were 23% and 62% of centres reported staff smoked with service users. Just over half (52%) reported screening and recording smoking status and 58% made referrals to Stop Smoking Services (SSS), although established links with SSS were low (12%) and most centres did not provide staff training on supporting smoking cessation. Areas of good practice included regular offers of smoking cessation support embedded in routine health reviews or visits from SSS and offering tangible harm reduction support. Areas for improvement include staff training, staff smoking with service users and skipping routine screening questions around smoking.

Conclusions

Smoking is accounted for across different policy types and restricted in some areas within most settings. Smoking cessation support is not routinely offered across the sector and there is little involvement with the SSS.
Acute cannabinoids impair association learning via selectively enhancing synaptic transmission in striatonigral neurons
Authors: Wu Meilin , Di Yuanyuan , Diao Zhijun , Yan Chuanting , Cheng Qiangqiang , Huang Huan , Liu Yingxun , Wei Chunling , Zheng Qiaohua , Fan Juan , Han Jing , Liu Zhiqiang , Tian Yingfang , Duan Haijun , Ren Wei , Sun Zongpeng
Published: May 2022

Background

Cannabinoids and their derivatives attract strong interest due to the tremendous potential of their psychoactive effects for treating psychiatric disorders and symptoms. However, their clinical application is restricted by various side-effects such as impaired coordination, anxiety, and learning and memory disability. Adverse impact on dorsal striatum-dependent learning is an important side-effect of cannabinoids. As one of the most important forms of learning mediated by the dorsal striatum, reinforcement learning is characterized by an initial association learning phase, followed by habit learning. While the effects of cannabinoids on habit learning have been well-studied, little is known about how cannabinoids influence the initial phase of reinforcement learning.

Results

We found that acute activation of cannabinoid receptor type 1 (CB1R) by the synthetic cannabinoid HU210 induced dose-dependent impairment of association learning, which could be alleviated by intra-dorsomedial striatum (DMS) injection of CB1R antagonist. Moreover, acute exposure to HU210 elicited enhanced synaptic transmission in striatonigral “direct” pathway medium spiny neurons (MSNs) but not indirect pathway neurons in DMS. Intriguingly, enhancement of synaptic transmission that is also observed after learning was abolished by HU210, indicating cannabinoid system might disrupt reinforcement learning by confounding synaptic plasticity normally required for learning. Remarkably, the impaired response-reinforcer learning was also induced by selectively enhancing the D1-MSN (MSN that selectively expresses the dopamine receptor type 1) activity by virally expressing excitatory hM3Dq DREADD (designer receptor exclusively activated by a designer drug), which could be rescued by specifically silencing the D1-MSN activity via hM4Di DREADD.

Conclusion

Our findings demonstrate dose-dependent deleterious effects of cannabinoids on association learning by disrupting plasticity change required for learning associated with the striatal direct pathway, which furthers our understanding of the side-effects of cannabinoids and the underlying mechanisms.
Sustained correction of hippocampal neurogenic and cognitive deficits after a brief treatment by Nutlin-3 in a mouse model of fragile X syndrome
Authors: Javadi Sahar , Li Yue , Sheng Jie , Zhao Lucy , Fu Yao , Wang Daifeng , Zhao Xinyu
Published: May 2022

Background

Fragile X syndrome (FXS), the most prevalent inherited intellectual disability and one of the most common monogenic forms of autism, is caused by a loss of fragile X messenger ribonucleoprotein 1 (FMR1). We have previously shown that FMR1 represses the levels and activities of ubiquitin ligase MDM2 in young adult FMR1-deficient mice, and treatment by a MDM2 inhibitor Nutlin-3 rescues both hippocampal neurogenic and cognitive deficits in FMR1-deficient mice when analyzed shortly after the administration. However, it is unknown whether Nutlin-3 treatment can have long-lasting therapeutic effects.

Methods

We treated 2-month-old young adult FMR1-deficient mice with Nutlin-3 for 10 days and then assessed the persistent effect of Nutlin-3 on both cognitive functions and adult neurogenesis when mice were 6-month-old mature adults. To investigate the mechanisms underlying the persistent effects of Nutlin-3, we analyzed the proliferation and differentiation of neural stem/progenitor cells isolated from these mice and assessed the transcriptome of the hippocampal tissues of treated mice.

Results

We found that transient treatment with Nutlin-3 of 2-month-old young adult FMR1-deficient mice prevents the emergence of neurogenic and cognitive deficits in mature adult FXS mice at 6 months of age. We further found that the long-lasting restoration of neurogenesis and cognitive function might not be mediated by changing intrinsic properties of adult neural stem cells. Transcriptomic analysis of the hippocampal tissue demonstrated that transient Nultin-3 treatment leads to significant expression changes in genes related to the extracellular matrix, secreted factors, and cell membrane proteins in the FMR1-deficient hippocampus.

Conclusions

Our data indicates that transient Nutlin-3 treatment in young adults leads to long-lasting neurogenic and behavioral changes likely through modulating adult neurogenic niche that impact adult neural stem cells. Our results demonstrate that cognitive impairments in FXS may be prevented by an early intervention through Nutlin-3 treatment.
Activation of the chemokine receptor 3 pathway leads to a better response to immune checkpoint inhibitors in patients with metastatic urothelial carcinoma
Authors: Feng Wenqin , Lin Anqi , Sun Le , Wei Ting , Ying Haoxuan , Zhang Jian , Luo Peng , Zhu Weiliang
Published: May 2022

Immune checkpoint inhibitors (ICIs) have made important breakthrough in anti-tumor therapy, however, no single biomarker can accurately predict their efficacy. Studies have found that tumor microenvironment is a key factor for determining the response to ICI therapy. Cytokine receptor 3 (C-X-C Motif Chemokine Receptor 3, CXCR3) pathway has been reported to play an important role in the migration, activation, and response of immune cells. We analyzed survival data, genomics, and clinical data from patients with metastatic urothelial carcinoma (mUC) who received ICI treatment to explore the relationship between CXCR3 pathway activation and the effectiveness of ICIs. The Cancer Genome Atlas Bladder Urothelial Carcinoma cohort and six other cohorts receiving ICI treatment were used for mechanism exploration and validation. In the ICI cohort, we performed univariate and multivariate COX analyses and discovered that patients in the CXCR3-high group were more sensitive to ICI treatment. A Kaplan–Meier analysis demonstrated that patients in the high CXCR3-high group had a better prognosis than those in the CXCR3-low group (P = 0.0001, Hazard Ratio = 0.56; 95% CI 0.42−0.75). CIBERSORT analysis found that mUC patients in the CXCR3-high group had higher levels of activated CD8+ T cells, M1 macrophages, and activated NK cells and less regulatory T cell (Treg) infiltration. Immunogenicity analysis showed the CXCR3-high group had higher tumor neoantigen burden (TNB). Our study suggests that CXCR3 pathway activation may be a novel predictive biomarker for the effectiveness of immunotherapy in mUC patients.
CDK4/6 inhibitors sensitize gammaherpesvirus-infected tumor cells to T-cell killing by enhancing expression of immune surface molecules
Authors: Wu Yiquan , Shrestha Prabha , Heape Natalie M. , Yarchoan Robert
Published: May 2022

Background

The two oncogenic human gammaherpesviruses, Kaposi sarcoma-associated herpesvirus (KSHV) and Epstein–Barr virus (EBV), both downregulate immune surface molecules, such as MHC-I, ICAM-1, and B7-2, enabling them to evade T-cell and natural killer cell immunity. Both also either encode for human cyclin homologues or promote cellular cyclin activity, and this has been shown to be important for proliferation and survival of gammaherpesvirus-induced tumors. CDK4/6 inhibitors, which are approved for certain breast cancers, have been shown to enhance expression of MHC-I in cell lines and murine models of breast cancer, and this was attributed to activation of interferons by endogenous retrovirus elements. However, it was not known if this would occur in gammaherpesvirus-induced tumors in which interferons are already activated.

Methods

Multiple KSHV/EBV-infected cell lines were treated with CDK4/6 inhibitors. The growth of viable cells and expression of surface markers was assessed. T cell activation stimulated by the treated cells was assayed by a T-cell activation bioassay. Both viral and host gene expression was surveyed using RT-qPCR.

Results

Three CDK4/6 inhibitors, abemaciclib, palbociclib, and ribociclib, inhibited cell growth in KSHV-induced primary effusion lymphoma (PEL) and EBV positive Burkitt’s lymphoma (BL) cell lines, and KSHV-infected human umbilical vein endothelial cells (HUVECs). Moreover, CDK4/6 inhibitors increased mRNA and surface expression of MHC-I in all three and prevented downregulation of MHC-I surface expression during lytic replication in KSHV-infected cells. CDK4/6 inhibitors also variably increased mRNA and surface expression of ICAM-1 and B7-2 in the tested lines. Abemaciclib also significantly enhanced T-cell activation induced by treated PEL and BL cells. Certain gammaherpesvirus genes as well as endogenous retrovirus (ERV) 3–1 genes were enhanced by CDK4/6 inhibitors in most PEL and BL lines and this enhancement was associated with expression of gamma interferon-induced genes including MHC-I.

Conclusions

These observations provide evidence that CDK4/6 inhibitors can induce expression of surface immune markers MHC-I, B7-2, and ICAM-1 in gammaherpesvirus-infected cell lines and induce virus-specific immunity. They can thus thwart virus-induced immune evasion. These effects, along with their direct effects on KSHV- or EBV-induced tumors, provide a rational for the clinical testing of these drugs in these tumors.
Recommendations for addressing the translational gap between experimental and clinical research on amyloid diseases
Authors: Solomon Miriam , Foderà Vito , Langkilde Annette Eva , Elliott Perry , Tagliavini Fabrizio , Forsyth Trevor , Klementieva Oxana , Bellotti Vittorio
Published: May 2022

This paper is a report of recommendations for addressing translational challenges in amyloid disease research. They were developed during and following an international online workshop organized by the LINXS Institute of Advanced Neutron and X-Ray Science in March 2021. Key suggestions include improving cross-cultural communication between basic science and clinical research, increasing the influence of scientific societies and journals (vis-à-vis funding agencies and pharmaceutical companies), improving the dissemination of negative results, and strengthening the ethos of science.
Plasma Torquetenovirus (TTV) microRNAs and severity of COVID-19
Authors: Stincarelli Maria Alfreda , Baj Andreina , Guidotti Bernardo , Spezia Pietro Giorgio , Novazzi Federica , Lucenteforte Ersilia , Tillati Silvia , Focosi Daniele , Maggi Fabrizio , Giannecchini Simone
Published: May 2022

Background

Torquetenovirus (TTV), a widespread anellovirus recognized as the main component of the healthy human virome, displays viremia that is highly susceptible to variations in immune competence. TTV possesses microRNA (miRNA)-coding sequences that might be involved in viral immune evasion. Among TTV-encoded miRNAs, miRNA t1a, t3b, and tth8 have been found in biological fluids. Here, the presence of TTV DNA and TTV miRNAs in the plasma of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected subjects was investigated to monitor the possible association with coronavirus disease 2019 (COVID-19) severity.

Methods

Detection of TTV DNA and miRNA t1a, t3b, and tth8 was investigated in plasma samples of 56 SARS-CoV-2-infected subjects with a spectrum of different COVID-19 outcomes. TTV DNA and TTV miRNAs were assessed with a universal single step real-time TaqMan PCR assay and miRNA quantitative RT-PCR miRNA assay, respectively.

Results

The TTV DNA prevalence was 59%, whereas at least one TTV miRNA was found in 94% of the patients tested. miRNA tth8 was detected in 91% of subjects, followed by miRNAs t3b (64%) and miRNAt1a (30%). Remarkably, although TTV DNA was unrelated to COVID-19 severity, miRNA tth8 was significantly associated with the degree of disease (adjusted incidence rate ratio (IRR) 2.04, 95% CI 1.14–3.63, for the subjects in the high severity group compared to those in the low severity group).

Conclusions

Our findings encourage further investigation to understand the potential role of TTV miRNAs in the different outcomes of COVID-19 at early and late stages.
Postoperative locoregional recurrence pattern and treatment management of stage pT4 sigmoid colon cancer: a retrospective cohort study
Authors: Lin Yaobin , Liu Shan , Hong Liang , Shao Lingdong , Wu Junxin
Published: May 2022

Background

This study aimed to explore the pattern of locoregional recurrence after surgery in patients with non-metastatic stage pT4 sigmoid colon cancer and the role of adjuvant radiotherapy on survival.

Methods

We retrospectively analyzed data from 208 patients who underwent surgery in our hospital. The patients were randomly divided into training and validation groups at a 1:1 ratio. Patients at high risk for locoregional recurrence were screened using Cox regression analysis. Based on the data of 2,886 patients in the Surveillance, Epidemiology, and End Results (SEER) database, the effect of adjuvant radiotherapy on overall survival (OS) and cancer-specific survival (CSS) was evaluated by Kaplan–Meier curves.

Results

Of the 208 patients, 57 (27.4%) presented with locoregional recurrences (14 anastomotic and 43 abdominal or pelvic lymph node recurrences). Multivariate analysis showed that serum CEA, differentiation, lymph node dissection number, and N stage were independent predictors of locoregional recurrence-free survival (all p < 0.05). A risk-stratification model was constructed, and a total score of ≥ 6.5 points was considered the high-risk group for locoregional recurrence. Both the training and validation sets presented that the model had a good predictive ability (area under the curve = 0.828 and 0.724, respectively). Analysis of SEER data revealed that adjuvant radiotherapy significantly prolonged OS and CSS in the high-risk population (all p < 0.05, vs. no radiotherapy).

Conclusions

Patients with a total risk score of 6.5 or more had a high likelihood of locoregional recurrence, and perhaps adjuvant radiotherapy could improve their survival.
Three-dimensional mapping study of pure transverse acetabular fractures
Authors: Li Junran , Zhai Jingxiu , Yin Yingchao , Tian Siyu , Wang Zhongzheng , Li Ligeng , Hou Zhiyong , Zhang Yingze
Published: May 2022

Background

To describe and analyze the morphological characteristics, location and frequency of pure transverse acetabular fracture lines through fracture mapping and quantitative measurements.

Methods

Transverse fractures were retrospectively reviewed and analyzed. All computed tomography (CT) data were used for reconstruction and manual reduction. The reductive fracture fragments were graphically overlaid onto a three-dimensional (3D) right hemipelvis template. Then, the fracture lines were accurately depicted onto the surface of the 3D template. The fracture lines were overlapped onto the model to create the 3D fracture map and heatmap. All cases were subdivided into infratectal (62-B1.1), juxtatectal (62-B1.2), and transtectal (62-B1.3) types based on the AO Foundation/Orthopedic Trauma Association (AO/OTA) classification. Some anatomic parameters of the transverse fractures were also analyzed in these 3 groups.

Results

Our study included forty-nine transverse fractures from 32 male and 17 female patients (mean age, 42 years; range 21–74 years) and included 19 type 62-B1.1, 17 type 62-B1.2, and 13 type 62-B1.3 fractures. The average anterior rim fracture angle was 70.0° (± 11.6°), and the posterior rim fracture angle was 92.4° (± 28.5°). The anterior rim fracture angles in 40 cases (40/49, 81.6%) fell within a wide range between 63° and 80°. On the heatmap, the hot zones were located on the highest position of the cotyloid fossa and the narrowed region, and the cold zone was on the inferior third of the articular surface. For type 62-B1.3 fractures, the hot zone was located on the posterior of the acetabular dome. There were no significant differences in anterior rim fracture angle and anterior height among the three patterns (P = 0.071,P = 0.072). Post hoc tests of the posterior rim fracture angle and the posterior height revealed significant differences among fracture subtypes (P < 0.01). The posterior intra-articular fracture line was significantly longer than the anterior intra-articular fracture line in type 62-B1.1 and type 62-B1.2 fractures (P < 0.01).

Conclusion

The fracture lines of transverse fractures through the anterior rim were concentrated on the narrowed zone, and the posterior fracture lines were diffusely distributed. The intra-articular fracture line distribution was focused on the superior and middle thirds of the joint surface. The recurrent fracture lines involving the weight-bearing dome mainly converged on the posterior region of the roof.
Hospital-onset sepsis and community-onset sepsis in critical care units in Japan: a retrospective cohort study based on a Japanese administrative claims database
Authors: Tonai Mayuko , Shiraishi Atsushi , Karumai Toshiyuki , Endo Akira , Kobayashi Hirotada , Fushimi Kiyohide , Hayashi Yoshiro
Published: May 2022

Background

Hospital- and community-onset sepsis are significant sepsis subgroups. Japanese data comparing these subgroups are limited. This study aimed to describe the epidemiology of hospital- and community-onset sepsis in critical care units in Japan.

Methods

We performed a retrospective cohort study using the Japanese Diagnosis and Procedure Combination database. Adult patients admitted to critical care units with sepsis from April 2010 to March 2020 were included. Sepsis cases were identified based on ICD-10 codes for infectious diseases, procedure codes for blood culture tests, and medication codes for antimicrobials. Patients’ characteristics, in-hospital mortality, and resource utilization were assessed. The in-hospital mortality between groups was compared using the Poisson regression generalized linear mixed-effect model.

Results

Of 516,124 patients, 52,183 (10.1%) had hospital-onset sepsis and 463,940 (89.9%) had community-onset sepsis. Hospital-onset sepsis was characterized by younger age, infrequent emergency hospitalization, frequent surgery under general anesthesia, and frequent organ support upon critical care unit admission compared to community-onset sepsis. In-hospital mortality was higher for hospital-onset than for community-onset sepsis (35.5% versus 19.2%; unadjusted mean difference, 16.3% [95% confidence interval (CI) 15.9–16.7]; adjusted mean difference, 15.6% [95% CI 14.9–16.2]). Mean hospital length of stay was longer for hospital-onset than for community-onset sepsis (47 days versus 30 days; unadjusted mean difference, 17 days [95% CI 16–17]; adjusted mean difference, 13 days [95% CI 12–14]).

Conclusion

Patients with hospital-onset sepsis admitted to critical care units in Japan had a poorer prognosis and more resource utilization including organ support rate, number of days with critical care unit surcharge codes, and hospital length of stay than those with community-onset sepsis.
Repair of acute respiratory distress syndrome by stromal cell administration (REALIST): a structured study protocol for an open-label dose-escalation phase 1 trial followed by a randomised, triple-blind, allocation concealed, placebo-controlled phase 2 trial
Authors: Gorman Ellen , Shankar-Hari Manu , Hopkins Phil , Tunnicliffe William S. , Perkins Gavin D. , Silversides Jonathan , McGuigan Peter , Jackson Colette , Boyle Roisin , McFerran Jamie , McDowell Cliona , Campbell Christina , McFarland Margaret , Smythe Jon , Thompson Jacqui , Williams Barry , Curley Gerard , Laffey John G. , Clarke Mike , McAuley Daniel F. , O’Kane Cecilia
Published: May 2022

Background

Mesenchymal stromal cells (MSCs) may be of benefit in ARDS due to immunomodulatory and reparative properties. This trial investigates a novel CD362 enriched umbilical cord derived MSC product (REALIST ORBCEL-C), produced to Good Manufacturing Practice standards, in patients with moderate to severe ARDS due to COVID-19 and ARDS due to other causes.

Methods

Phase 1 is a multicentre open-label dose-escalation pilot trial. Patients will receive a single infusion of REALIST ORBCEL-C (100 × 106 cells, 200 × 106 cells or 400 × 106 cells) in a 3 + 3 design. Phase 2 is a multicentre randomised, triple blind, allocation concealed placebo-controlled trial. Two cohorts of patients, with ARDS due to COVID-19 or ARDS due to other causes, will be recruited and randomised 1:1 to receive either a single infusion of REALIST ORBCEL-C (400 × 106 cells or maximal tolerated dose in phase 1) or placebo. Planned recruitment to each cohort is 60 patients. The primary safety outcome is the incidence of serious adverse events. The primary efficacy outcome is oxygenation index at day 7. The trial will be reported according to the Consolidated Standards for Reporting Trials (CONSORT 2010) statement.

Discussion

The development and manufacture of an advanced therapy medicinal product to Good Manufacturing Practice standards within NHS infrastructure are discussed, including challenges encountered during the early stages of trial set up. The rationale to include a separate cohort of patients with ARDS due to COVID-19 in phase 2 of the trial is outlined.

Trial registration

ClinicalTrials.gov NCT03042143. Registered on 3 February 2017. EudraCT Number 2017-000584-33
The Cancer Financial Experience (CAFÉ) study: randomized controlled trial of a financial navigation intervention to address cancer-related financial hardship
Authors: Henrikson Nora B. , Anderson Melissa L. , Dickerson John , Ewing John J. , Garcia Robin , Keast Erin , King Deborah A. , Lewis Cara , Locher Blake , McMullen Carmit , Norris Consuelo M. , Petrik Amanda F. , Ramaprasan Arvind , Rivelli Jennifer S. , Schneider Jennifer L. , Shulman Lisa , Tuzzio Leah , Banegas Matthew P.
Published: May 2022

Background

There is an urgent need for evidence on how interventions can prevent or mitigate cancer-related financial hardship. Our objectives are to compare self-reported financial hardship, quality of life, and health services use between patients receiving a financial navigation intervention versus a comparison group at 12 months follow-up, and to assess patient-level factors associated with dose received of a financial navigation intervention.

Methods

The Cancer Financial Experience (CAFÉ) study is a multi-site randomized controlled trial (RCT) with individual-level randomization. Participants will be offered either brief (one financial navigation cycle, Arm 2) or extended (three financial navigation cycles, Arm 3) financial navigation. The intervention period for both Arms 2 and 3 is 6 months. The comparison group (Arm 1) will receive enhanced usual care. The setting for the CAFÉ study is the medical oncology and radiation oncology clinics at two integrated health systems in the Pacific Northwest. Inclusion criteria includes age 18 or older with a recent cancer diagnosis and visit to a study clinic as identified through administrative data. Outcomes will be assessed at 12-month follow-up. Primary outcomes are self-reported financial distress and health-related quality of life. Secondary outcomes are delayed or foregone care; receipt of medical financial assistance; and account delinquency. A mixed methods exploratory analysis will investigate factors associated with total intervention dose received.

Discussion

The CAFÉ study will provide much-needed early trial evidence on the impact of financial navigation in reducing cancer-related financial hardship. It is theory-informed, clinic-based, aligned with patient preferences, and has been developed following preliminary qualitative studies and stakeholder input. By design, it will provide prospective evidence on the potential benefits of financial navigation on patient-relevant cancer outcomes. The CAFÉ trial’s strengths include its broad inclusion criteria, its equity-focused sampling plan, its novel intervention developed in partnership with clinical and operations stakeholders, and mixed methods secondary analyses related to intervention dose offered and dose received. The resulting analytic dataset will allow for rich mixed methods analysis and provide critical information related to implementation of the intervention should it prove effective.

Trial registration

ClinicalTrials.govNCT05018000. August 23, 2021.