bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and factors associated with diarrheal diseases among children below five years in selected slum settlements in Entebbe municipality, Wakiso district, Uganda
Authors: Nantege Robinah , Kajoba Dickson , Ddamulira Christopher , Ndoboli Fred , Ndungutse David
Published: July 2022

Background

Despite global interventions to prevent and control diarrhea, it still remains a public health problem leading to childhood morbidity and mortality majorly in developing countries. In Uganda, diarrhea is amongst the five leading causes of under-five mortality, contributing to more than 140,000 deaths every year and this accounts for 7.1% of all under-five mortalities in Uganda. Efforts to prevent and lower diarrheal diseases need to be informed by data on determinants of diarrhea. The study assessed factors associated with diarrheal diseases among children below five years in selected slum settlements in Entebbe municipality, Wakiso District, Uganda.

Methods

The study employed a cross-sectional study design covering 384 randomly selected households having children < 5 years old in the study area using quantitative research methods. Data was collected using close-ended questionnaires and diarrhea disease history was captured for the last month before the survey. Bivariate and multivariate logistic regression analyses were used to identify the risk factors associated with childhood diarrhea considering a 95% confidence level.

Results

The prevalence of Diarrhea disease in children among the selected slum settlements in Entebbe municipality was found to be at 62.4%. Access to water from a protected water source (deep well and borehole), presence of a vent in toilets, age, and child birth weight were found to be significantly associated with diarrheal diseases among children below five years in the selected slum settlements in Entebbe municipality.

Conclusion

The prevalence of childhood diarrhea among children < 5 years of age in selected slums of Entebbe municipality was found high. Use of water from a protected source, presence of a vent in toilets, age, child birth and weight were identified as predictors of diarrhea occurrence. These findings imply that community health education is urgently needed for fighting childhood diarrhea in the study area to eliminate the predisposing factors to diarrhea.
Prevalence of early skin-to-skin contact and its impact on exclusive breastfeeding during the maternity hospitalization
Authors: Giang Hoang Thi Nam , Duy Do Thi Thuy , Vuong Nguyen Lam , Ngoc Nguyen Thi Tu , Pham Thu Thi , Tuan Le Quang , Oai Le , Do Thuc Anh Pham , Khanh Ton That , Thi Nguyen Thi Anh , Luu Mai Ngoc , Nga Tran Thi Tuyet , Hieu Le Tho Minh , Huy Nguyen Tien
Published: July 2022

Background

Early essential newborn care has been implemented in countries regardless high or low neonatal mortality. This study aims to investigate the current practice of skin-to-skin contact (SSC) and its effect on exclusive breastfeeding during the hospital stay.

Methods

This is a cross-sectional study of 1812 Vietnamese mothers in multicenter. A questionnaire answered by the mothers was used to assess the duration of both SSC and breastfeeding practices. Multivariable logistic regression was used to identify a dose–response relationship between early SSC and prevalence of exclusive breastfeeding in hospital.

Results

There were 88.7% of mothers experiencing SSC with their infants right after birth and the highest prevalence of SSC was found in district hospitals. Among those experiencing SSC, 18.8% of the infants received more than 90 min of SSC and completed the first breastfeeding during SSC time. Prevalence of exclusive breastfeeding during maternity hospital stay was 46.7%. We found a significant dose–response relation between the duration of SSC and exclusive breastfeeding in hospital. Compared with infants without SSC, the prevalence of exclusive breastfeeding was higher in infants who experienced SSC for 15–90 min (adjusted odds ratio [aOR], 95% confidence interval [95%-CI]: 2.62 [1.61–4.27]) and more than 90 min (aOR [95%-CI]: 5.98 [3.48–10.28]). Completed first breastfeeding during SSC time (aOR [95%-CI]: 4.24 [3.28–5.47]) and being born in district hospitals (aOR [95%-CI]: 2.35 [1.79–3.09]) were associated with increased prevalence of exclusive breastfeeding during hospital stay. On the other hand, mother education level as high school/intermediate (aOR [95%-CI]: 0.58 [0.42–0.82]) and place of residence classified as rural decreased odds of exclusive breastfeeding in hospital (aOR [95%-CI]: 0.78 [0.61–0.99]).

Conclusion

Our results demonstrate a strong dose–response relationship between duration of SSC and exclusive breastfeeding in hospital. Interventions that support exclusive breastfeeding during hospital stay, especially achieving prolonged uninterrupted SSC, could improve the duration of breastfeeding.
Multisystem inflammatory syndrome in a neonate with severe hemophilia - a diagnostic challenge in COVID times: a case report
Authors: Arun Sumitha , Cherian Taliya Grace , Philip Chepsy
Published: July 2022

Background

Multisystem Inflammatory Syndrome in Neonates (MIS-N) can occur following antenatal COVID- 19 infection in the mother. Here we report a rare case of a neonate with Hemophilia A and MIS-N.

Case presentation

A 2-day-old baby presented with an intramuscular hematoma, neonatal seizures, and isolated activated partial thromboplastin time (APTT) prolongation. The neurosonogram showed a subdural hematoma. A diagnosis of Hemophilia A was made and was confirmed by factor 8 assay and genetic analysis. Supportive measures and Factor 8 replacement was initiated. A rising trend of inflammatory markers and an ongoing need for mechanical ventilation were noted. As there was a history of COVID-19 in the mother in the third trimester, MIS-N was diagnosed. The baby was treated with intravenous immunoglobulin (IVIG) and steroids, and there was an improvement in the clinical and laboratory markers. However, the baby developed seizures on day 16. There was an increase in the subdural hemorrhage and a further rise in inflammatory markers. A craniostomy and hematoma evacuation was done and the baby improved.

Conclusion

The concurrent occurrence of hemophilia A with intracranial bleed, and MIS-N in a neonate is a diagnostic challenge. It is important to have a high index of suspicion to ensure timely diagnosis and treatment of MIS-N in this pandemic era.
The professed effect of stigma on community psychiatric nurses in the Greater Accra region of Ghana
Authors: Buertey Abigail Ansere
Published: July 2022

Background

Stigma is a major factor that inhibits Mental Health Nurses work, especially Community Psychiatric Nurses, in terms of productivity. Even though mental health services have improved drastically, because of decentralization of mental health care, a lot more people still have reservations when it comes to mental health nurses particularly Community Psychiatric Nurses. The purpose of the study was to explore the professed effects of stigma on CPNs in the Southern part of Ghana.

Methods

The study was carried out in three district hospitals (Ga South, Ga Central and Okaikoi) all in the Accra Metropolis. The aim of the study was to describe how stigma affects Community Psychiatric Nurses. A qualitative descriptive exploratory design was adopted for the study. The purposive sampling technique was used to recruit participants. Data was saturated with 12 participants, aged between 25 and 40 years. The audio-taped interviews were transcribed verbatim and afterwards analyzed using thematic and content analysis.

Results

The findings gathered from participants revealed that Community Psychiatric Nurses experienced various effects of stigma, such as low productivity, depression, and anger. Most of the participants recounted how stigmatization had affected their work both in the hospital setting and in their communities.

Conclusion

The study showed that Community Psychiatric Nurses carried out their activities with much difficulty, because of their poor image. They stressed the need for recognition and support from employers, stakeholders and the general community so as to boost confidence and morale with the resultant effect of better healthcare delivery.
Quantitative analysis of facial symmetry by using three-dimensional technology
Authors: Wu Zhouqiang , Gao Xiaolei , Long Hu , Lai Wenli
Published: July 2022

Background

Facial symmetry is becoming increasingly important in today's orthodontic treatment. But the asymmetrical boundary is not clearly demarcated. Stereophotogrammetry has a clear advantage in measuring facial asymmetry. The aim of this study was to quantify the facial asymmetry by three-dimensional (3D) technology as well as to study whether the evaluation by non-experts about facial asymmetry was consistent with the analysis by 3D technology.

Methods

The facial symmetry of 330 patients was evaluated by 10 non-experts. 3D facial images were taken using 3dMD stereophotogrammetry equipment. The original face and its mirror shell were divided into 7 regions and the surface matching was measured in the whole face and all regional areas. The degree of symmetry was calculated by the software 3-matic STL 9.0. The difference between the two groups was analyzed by Independent-Samples T Test and the diagnostic efficiency of symmetry degree was analyzed by ROC curve analysis. The consistency between the symmetric degree and the result of evaluation was analyzed by Pearson correlation analysis.

Results

The ROC analysis revealed significant diagnostic values in the determination of the facial asymmetry of lip, chin, cheek and lateral mandible areas. The cut-off values of symmetry degree were between 60 and 80%. The evaluation was middle correlation with the symmetric degree of the whole face.

Conclusions

The chin and lateral mandible contribute most significantly to the facial symmetry. The objective measurement of facial symmetry, 3D technology, is reliable.
Comprehensive surgical treatment for obstructive rectal endometriosis: a case report and review of the literature
Authors: Xu Yumei , Xu Yixin , Miao Lu , Cao Meng , Xu Wei , Shi Linsen
Published: July 2022

Background

Intestinal obstruction caused by endometriosis maybe easily misdiagnosed as a tumor or other occupying disease in emergency condition. How to deal with it depending on the clarity of the preoperative diagnosis and the experience of the surgeon.

Case presentation

A 47-year-old woman, admitted to our emergency service with abdominal pain and distension for 5 days, anal stop exhausting and defecating for 3 days. Based on imaging and laboratory examination, we made a preoperative diagnosis of rectal endometriosis probably. After 7 days of colon decompression with a intestinal obstruction catheter, an operation of laparoscopic partial rectal and sigmoid resection without protective stoma and total hysterectomy was performed successfully. The patient obtained a smooth postoperative course and doing well after 12-weeks follow up.

Conclusions

Obstruction caused by rectal endometriosis is very rare and easily overlooked by surgeon and gynecologist. Appropriate preoperative diagnosis and preoperative management can reduce the trauma and incidence of complications.
The most appropriate cervical dilatation for massage to reduce labor pain and anxiety: a randomized clinical trial
Authors: Shahbazzadegan Samira , Nikjou Roya
Published: July 2022

Background

Managing labor pain by performing massage is one of the useful strategies to reduce the rate of cesarean section and increase the tendency of women for pregnancy. Therefore, it is necessary to determine the best time for massage therapy to reduce the labor pain and anxiety. In this regard, the present study was conducted to determine the cervical dilatation appropriate for performing massage in order to reduce the labor pain and anxiety.

Methods

This randomized clinical trial study was conducted on 60 nulliparous pregnant women. Eligible participants with active phase of labor were divided randomly into two groups. The intervention group received the massage three times in of dilatation 5–7–9 cm for 20 min each time by same person without the use of oil in the LDR, based on Kimber massage instructions. In the control group, all routine care was performed except massage. Pain intensity was assessed using pain ruler. Demographic and anxiety data were collected through questionnaires.

Results

The difference between the mean pains in the studied groups was significant in 7 cm (p < 0.0001) of cervical dilatation but was not significant in 5 cm (p = 0.084) and 9 cm (p = 0.591) dilatation. Massage effectively decreased pain intensity. The mean maternal anxiety was not significant at the beginning of the study, but was significant after performing massage (p < 0.0001) and anxiety score in the massage group decreased from 63.36 ± 5.28 (severe anxiety) at the beginning to 42.60 ± 5.83 (moderate anxiety) at the end of the study. In the control group, it increased from 66.33 ± 7.66 to 67.1 ± 5.65.

Conclusion

The appropriate dilatation of cervix for massage in order to reduce labor pain was observed in 7 cm. Also, massage had a significant effect on reducing anxiety. Therefore, massage is recommended as a routine care in 7 cm cervical dilatations.

Trial registration

This trial was registered with the Iran Trial Center (trial ID: IRCT20140118016255N5).https://en.irct.ir/trial/28120
Healthcare workers’ perspectives on access to sexual and reproductive health services in the public, private and private not-for-profit sectors: insights from Kenya, Tanzania, Uganda and Zambia
Authors: Ooms Gaby I. , van Oirschot Janneke , Okemo Dorothy , Reed Tim , van den Ham Hendrika A. , Mantel-Teeuwisse Aukje K.
Published: July 2022

Background

Access to sexual and reproductive health services remains a challenge for many in Kenya, Tanzania, Uganda and Zambia. Health service delivery in the four countries is decentralised and provided by the public, private and private not-for-profit sectors. When accessing sexual and reproductive health services, clients encounter numerous challenges, which might differ per sector. Healthcare workers have first-hand insight into what impediments to access exist at their health facility. The aim of this study was to identify differences and commonalities in barriers to access to sexual and reproductive health services across the public, private and private not-for-profit sectors.

Methods

A cross-sectional survey was conducted among healthcare workers working in health facilities offering sexual and reproductive health services in Kenya (n = 212), Tanzania (n = 371), Uganda (n = 145) and Zambia (n = 243). Data were collected in July 2019. Descriptive statistics were used to describe the data, while binary logistic regression analyses were used to test for significant differences in access barriers and recommendations between sectors.

Results

According to healthcare workers, the most common barrier to accessing sexual and reproductive health services was poor patient knowledge (37.1%). Following, issues with supply of commodities (42.5%) and frequent stockouts (36.0%) were most often raised in the public sector; in the other sectors these were also raised as an issue. Patient costs were a more significant barrier in the private (33.3%) and private not-for-profit sectors (21.1%) compared to the public sector (4.6%), and religious beliefs were a significant barrier in the private not-for-profit sector compared to the public sector (odds ratio = 2.46, 95% confidence interval = 1.69–3.56). In all sectors delays in the delivery of supplies (37.4-63.9%) was given as main stockout cause. Healthcare workers further believed that it was common that clients were reluctant to access sexual and reproductive health services, due to fear of stigmatisation, their lack of knowledge, myths/superstitions, religious beliefs, and fear of side effects. Healthcare workers recommended client education to tackle this.

Conclusions

Demand and supply side barriers were manifold across the public, private and private not-for-profit sectors, with some sector-specific, but mostly cross-cutting barriers. To improve access to sexual and reproductive health services, a multi-pronged approach is needed, targeting client knowledge, the weak supply chain system, high costs in the private and private not-for-profit sectors, and religious beliefs.
Associations of thiazide use with skin cancers: a systematic review and meta-analysis
Authors: Shao Shih-Chieh , Lai Chien-Cheng , Chen Yi-Hung , Lai Edward Chia-Cheng , Hung Ming-Jui , Chi Ching-Chi
Published: July 2022

Background

Previous findings on the associations of thiazide use with skin cancers were conflicting. This study aimed to examine the associations of individual thiazide use with skin cancer risk, differentiated by subtypes of skin cancers, geographic regions, and cumulative doses of individual thiazides.

Methods

We searched PubMed, Embase, and Cochrane Central Register of Controlled Trials for relevant studies on January 5, 2022, scanned the references of included studies, and consulted experts. We included case-control and cohort studies or randomized trials reporting the associations of individual thiazide or thiazide-like diuretics use with skin cancers. Non-melanoma skin cancer (NMSC) and melanoma were analysed separately. A random-effects model meta-analysis was conducted for pooled odds ratio (OR) and hazard ratio (HR) for skin cancers related to individual thiazide use.

Results

We included 15, 5, and 5 case-control or cohort studies reporting the risk for skin cancers associated with hydrochlorothiazide, bendroflumethiazide, and indapamide use, respectively, with 17,848,313 participants. The meta-analysis showed associations of hydrochlorothiazide use with increased risk of NMSC (OR 1.16, 95% CI 1.08–1.24; HR 1.26, 95% CI 1.04–1.54), squamous cell carcinoma (SCC) (OR 1.32, 95% CI 1.06–1.65; HR 1.61, 95% CI 0.97–2.67), and melanoma (OR 1.11, 95% CI 1.02–1.20; HR 1.03, 95% CI 0.93–1.14). The increased risks for SCC were associated with high cumulative doses of hydrochlorothiazide (OR 2.56, 95% CI 1.43–4.57; HR 1.20, 95% CI 1.00–1.45). Hydrochlorothiazide use was associated with different subtypes of melanoma including superficial spreading (OR 1.18, 95% CI 1.05–1.33), nodular (OR 1.23, 95% CI 1.08–1.39), and lentigo maligna melanoma (OR 1.33, 95% CI 1.08–1.65). Various cumulative doses of hydrochlorothiazide were associated with increased odds for melanoma. However, the associations of hydrochlorothiazide use with increased risk of NMSC and melanoma only appeared in non-Asian countries. No meaningful increase in the risk for skin cancers was associated with bendroflumethiazide and indapamide.

Conclusions

Hydrochlorothiazide is associated with an increased risk for NMSC (especially SCC) and melanoma in non-Asian countries, whereas bendroflumethiazide and indapamide are not associated with a meaningful risk for skin cancers. Healthcare professionals and patients should be informed of the different risk profiles of skin cancers associated with different thiazides, cumulative doses, and regions.

Trial registration

PROSPERO CRD42021234317.
Leveraging geo-referenced malaria information to increase domestic financial support for malaria elimination in Thailand
Authors: Sudathip Prayuth , Dharmarak Pratin , Rossi Sara , Promda Nutthawoot , Newby Gretchen , Larson Erika , Gopinath Deyer , Kanjanasuwan Jerdsuda , Promeiang Praparat , Lertpiriyasuwat Cheewanan , Areechokchai Darin , Prempree Preecha
Published: July 2022

Thailand’s National Malaria Elimination Strategy 2017–2026 seeks to increase domestic support and financing for malaria elimination. During 2018–2020, through a series of training sessions, public health officials in Thailand utilized foci-level malaria data to engage subdistrict-level government units known as Local Administrative Organizations (LAOs) with the aim of increasing their understanding of their local malaria situation, collaboration with public health networks, and advocacy for financial support of targeted interventions in villages within their jurisdictions. As a result of these efforts, total LAO funding support for malaria nearly doubled from the 2017 baseline to 2020. In 2021, a novel “LAO collaboration” feature was added to Thailand’s national malaria information system that enables tracking and visualization of LAO financial support of malaria in areas with transmission, by year, down to the subdistrict level. This case study describes Thailand’s experience implementing the LAO engagement strategy, quantifying and monitoring the financial support mobilized from LAOs, and results from a qualitative study in five high-performance provinces examining factors and approaches that foster successful local collaboration between LAOs, public health networks, and communities for malaria prevention and response. Results from the study showed that significant malaria endemicity or local outbreaks helped spur collaboration in multiple provinces. Increases in LAO support and involvement were attributable to four approaches employed by public health officials: (a) strengthening malaria literacy and response capacity of LAOs, (b) organizational leadership in response to outbreaks, (c) utilization of structural incentives, and (d) multisectoral involvement in malaria response. In two provinces, capacity building of LAOs in malaria vector control, following a precedent set by Thailand’s dengue programme, enabled LAO personnel to play both funding and implementation roles in local malaria response. Wider replication of the LAO engagement strategy across Thailand may sustain gains and yield efficiencies in the fight against malaria as the vector-borne disease workforce declines. Lessons from Thailand’s experience may be useful for malaria programmes in other geographies to support the goals and sustainability of elimination and prevention of re-establishment by improving financing through local collaboration between the health system and elected officials.
A universal precautions approach to reducing stigma in health care: getting beyond HIV-specific stigma
Authors: Treloar Carla , Cama Elena , Lancaster Kari , Brener Loren , Broady Timothy R. , Cogle Aaron , O’Donnell Darryl
Published: July 2022

Background

Delivery of effective health care is hampered by stigma, the social processes that attach negative judgement and response to some attributes, conditions, practices and identities. Experiencing or anticipating stigma can lead to a range of practical impacts, including avoidance of health care. While we are concerned about the stigma that is attached to HIV, this commentary makes the argument that the health system is burdened by stigma of many origins.

Main body

Reducing stigma is a key issue in improving quality of health care. Our focus on HIV is about providing better care in a non-judgemental, respectful and dignified manner which enhances the health and well-being of individuals as well as delivering benefit to society at large through better population health outcomes. However, the same could be said for the numerous possible attributes, conditions, practices and identities that attract stigma. It is unrealistic to expect health systems to respond to siloed appeals for change and action. A unifying logic is needed to propel concerns about stigma to the front of the queue for action by health systems.

Conclusion

This commentary suggests the need for a universal precautions approach to stigma in health care, that focuses on recognising that all people may experience stigma and discrimination targeted at one or more aspects of their identities, attributes, practices and health conditions. Drawing on health system precepts of equity, access and quality of care, we argue that a universal precautions approach to reducing stigma of all origins can effect everyday aspects of policy, procedure and practice to improve outcomes for individuals and for population health.
Postoperative recurrent patterns of gallbladder cancer: possible implications for adjuvant therapy
Authors: Yuan Zhijun , Shui Yongjie , Liu Lihong , Guo Yinglu , Wei Qichun
Published: July 2022

Background

Gallbladder cancer (GBC) is an uncommon malignancy with high recurrent rate and poor prognosis. This study investigates the recurrent patterns of postoperative GBC, with the aim to guide the adjuvant treatments, including the radiotherapy.

Methods

Retrospectively analyzed the 109 GBC patients who underwent surgery in our institution from January 2013 to 2018. Clinical follow-up revealed 54 recurrent cases, of which 40 had detailed locations of recurrence. The sites of recurrence were recorded and divided into the tumor bed, corresponding lymphatic drainage area, intrahepatic recurrence, and the other distant metastasis.

Results

The median follow-up time is 34 months (IQR: 11–64). The median disease-free survival (DFS) and overall survival (OS) were 48.8 months and 53.7 months, respectively. Through univariate analysis, risk factors for DFS and OS include tumor markers (CA199 and CEA), hepatic invasion, perineural invasion, lymphovascular invasion, TNM staging and tumor differentiation. Through multivariate analysis, risk factors for DFS include hepatic invasion and TNM staging, and for OS is TNM staging only. Of the 40 cases with specific recurrent sites, 29 patients (29/40, 72.5%) had recurrence in the potential target volume of postoperative radiotherapy (PORT), which include tumor bed and corresponding lymphatic drainage area. The common recurrent lymph node groups included abdominal para-aortic lymph node (No.16, 15/29), hepatoduodenal ligament lymph node (No.12, 8/29), retro-pancreatic head lymph node (No.13, 7/29) and celiac axis lymph node (No.9, 4/29). Twenty cases with recurrences inside the potential PORT target volume were accompanied by distant metastasis. Another 11 cases had distant metastasis alone, so totally 31 cases developed distant metastasis (31/40, 77.5%), including 18 cases with hepatic metastasis.

Conclusion

The recurrence and metastasis rates are high in GBC and adjuvant therapy is needed. Up to 75% of the recurrent cases occurred in the potential target volume of postoperative radiotherapy, suggesting that postoperative radiotherapy has the possible value of improving local-regional control. The potential target volume of radiotherapy should include the tumor bed, No.8, No.9, No.11, No.12, No.13, No.14, No. 16a2, No. 16b1 lymph node groups.
Predicting for anti-(mutant) SARS-CoV-2 and anti-inflammation compounds of Lianhua Qingwen Capsules in treating COVID-19
Authors: Hong Liang , He Min , Li Shaoping , Zhao Jing
Published: July 2022

Background

Lianhua Qingwen Capsules (LHQW) is a traditional Chinese medicine prescription commonly used to treat viral influenza in China. There has been sufficient evidence that LHQW could effectively treat COVID-19. Nevertheless, the potential anti-(mutant) SARS-CoV-2 and anti-inflammation compounds in LHQW are still vague.

Methods

The compounds of LHQW and targets were collected from TCMSP, TCMID, Shanghai Institute of Organic Chemistry of CAS database, and relevant literature. Autodock Vina was used to carry out molecular docking. The pkCSM platform to predict the relevant parameters of compound absorption in vivo. The protein–protein interaction (PPI) network was constructed by the STRING database. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was carried out by Database for Annotation, Visualization, and Integrated Discovery (DAVID). The anti-(mutant) SARS-CoV-2 and anti-inflammation networks were constructed on the Cytoscape platform.

Results

280 compounds, 16 targets related to SARS-CoV-2, and 54 targets related to cytokine storm were obtained by screening. The key pathways Toll-like receptor signaling, NOD-like receptor signal pathway, and Jak-STAT signaling pathway, and the core targets IL6 were obtained by PPI network and KEGG pathway enrichment analysis. The network analysis predicted and discussed the 16 main anti-SARS-CoV-2 active compounds and 12 main anti-inflammation active compounds. Ochnaflavone and Hypericin are potential anti-mutant virus compounds in LHQW.

Conclusions

In summary, this study explored the potential anti-(mutant) SARS-CoV-2 and anti-inflammation compounds of LHQW against COVID-19, which can provide new ideas and valuable references for discovering active compounds in the treatment of COVID-19.
21q22 amplification detection in three patients with acute myeloid leukemia: cytogenomic profiling and literature review
Authors: Kudalkar Emily M. , Pang Changlee , Haag Mary M. , Pollyea Daniel A. , Kamdar Manali , Xu Gang , Su Meng , Carstens Billie , Swisshelm Karen , Bao Liming
Published: July 2022

Background

21q22 amplification is a rare cytogenetic aberration in acute myeloid leukemia (AML). So far, the cytogenomic and molecular features and clinical correlation of 21q22 amplification in AML have not been well-characterized.

Case presentation

Here, we describe a case series of three AML patients with amplified 21q22 identified by fluorescence in situ hybridization using a RUNX1 probe. Two of these patients presented with therapy-related AML (t-AML) secondary to chemotherapy, while the third had de novo AML. There was one case each of FAB M0, M1 and M4. Morphologic evidence of dysplasia was identified in both t-AML cases. Phenotypic abnormalities of the myeloblasts were frequently observed. Extra copies of 21q22 were present on chromosome 21 and at least one other chromosome in two cases. Two showed a highly complex karyotype. Microarray analysis of 21q22 amplification in one case demonstrated alternating levels of high copy number gain split within the RUNX1 locus at 21q22. The same patient also had mutated TP53. Two patients died at 1.5 and 11 months post-treatment, while the third elected palliative care and died within 2 weeks.

Conclusions

Our results provide further evidence that 21q22 amplification in AML is associated with complex karyotypes, TP53 aberrations, and poor outcomes. Furthermore, we demonstrate that 21q22 amplification is not always intrachromosomally localized to chromosome 21 and could be a result of structural aberrations involving 21q22 and other chromosomes.
Development and validation of a multivariable prediction model of central venous catheter-tip colonization in a cohort of five randomized trials
Authors: Iachkine Jeanne , Buetti Niccolò , de Grooth Harm-Jan , Briant Anaïs R. , Mimoz Olivier , Mégarbane Bruno , Mira Jean-Paul , Ruckly Stéphane , Souweine Bertrand , du Cheyron Damien , Mermel Leonard A. , Timsit Jean-François , Parienti Jean-Jacques
Published: July 2022

Background

The majority of central venous catheters (CVC) removed in the ICU are not colonized, including when a catheter-related infection (CRI) is suspected. We developed and validated a predictive score to reduce unnecessary CVC removal.

Methods

We conducted a retrospective cohort study from five multicenter randomized controlled trials with systematic catheter-tip culture of consecutive CVCs. Colonization was defined as growth of ≥103 colony-forming units per mL. Risk factors for colonization were identified in the training cohort (CATHEDIA and 3SITES trials; 3899 CVCs of which 575 (15%) were colonized) through multivariable analyses. After internal validation in 500 bootstrapped samples, the CVC-OUT score was computed by attaching points to the robust (> 50% of the bootstraps) risk factors. External validation was performed in the testing cohort (CLEAN, DRESSING2 and ELVIS trials; 6848 CVCs, of which 588 (9%) were colonized).

Results

In the training cohort, obesity (1 point), diabetes (1 point), type of CVC (dialysis catheter, 1 point), anatomical insertion site (jugular, 4 points; femoral 5 points), rank of the catheter (second or subsequent, 1 point) and catheterization duration (≥ 5 days, 2 points) were significantly and independently associated with colonization . Area under the ROC curve (AUC) for the CVC-OUT score was 0.69, 95% confidence interval (CI) [0.67–0.72]. In the testing cohort, AUC for the CVC-OUT score was 0.60, 95% CI [0.58–0.62]. Among 1,469 CVCs removed for suspected CRI in the overall population, 1200 (82%) were not colonized. The negative predictive value (NPV) of a CVC-OUT score < 6 points was 94%, 95% CI [93%–95%].

Conclusion

The CVC-OUT score had a moderate ability to discriminate catheter-tip colonization, but the high NPV may contribute to reduce unnecessary CVCs removal. Preference of the subclavian site is the strongest and only modifiable risk factor that reduces the likelihood of catheter-tip colonization and consequently the risk of CRI.

Clinical Trials Registration: NCT00277888, NCT01479153, NCT01629550, NCT01189682, NCT00875069.
scSTEM: clustering pseudotime ordered single-cell data
Authors: Song Qi , Wang Jingtao , Bar-Joseph Ziv
Published: July 2022

We develop scSTEM, single-cell STEM, a method for clustering dynamic profiles of genes in trajectories inferred from pseudotime ordering of single-cell RNA-seq (scRNA-seq) data. scSTEM uses one of several metrics to summarize the expression of genes and assigns ap-value to clusters enabling the identification of significant profiles and comparison of profiles across different paths. Application of scSTEM to several scRNA-seq datasets demonstrates its usefulness and ability to improve downstream analysis of biological processes. scSTEM is available athttps://github.com/alexQiSong/scSTEM.
Identification of a cytokine-dominated immunosuppressive class in squamous cell lung carcinoma with implications for immunotherapy resistance
Authors: Yang Minglei , Lin Chenghao , Wang Yanni , Chen Kang , Zhang Haiyue , Li Weizhong
Published: July 2022

Background

Immune checkpoint blockade (ICB) therapy has revolutionized the treatment of lung squamous cell carcinoma (LUSC). However, a significant proportion of patients with high tumour PD-L1 expression remain resistant to immune checkpoint inhibitors. To understand the underlying resistance mechanisms, characterization of the immunosuppressive tumour microenvironment and identification of biomarkers to predict resistance in patients are urgently needed.

Methods

Our study retrospectively analysed RNA sequencing data of 624 LUSC samples. We analysed gene expression patterns from tumour microenvironment by unsupervised clustering. We correlated the expression patterns with a set of T cell exhaustion signatures, immunosuppressive cells, clinical characteristics, and immunotherapeutic responses. Internal and external testing datasets were used to validate the presence of exhausted immune status.

Results

Approximately 28 to 36% of LUSC patients were found to exhibit significant enrichments of T cell exhaustion signatures, high fraction of immunosuppressive cells (M2 macrophage and CD4 Treg), co-upregulation of 9 inhibitory checkpoints (CTLA4, PDCD1, LAG3, BTLA, TIGIT, HAVCR2, IDO1, SIGLEC7, and VISTA), and enhanced expression of anti-inflammatory cytokines (e.g. TGFβ and CCL18). We defined this immunosuppressive group of patients as exhausted immune class (EIC). Although EIC showed a high density of tumour-infiltrating lymphocytes, these were associated with poor prognosis. EIC had relatively elevated PD-L1 expression, but showed potential resistance to ICB therapy. The signature of 167 genes for EIC prediction was significantly enriched in melanoma patients with ICB therapy resistance. EIC was characterized by a lower chromosomal alteration burden and a unique methylation pattern. We developed a web application (http://lilab2.sysu.edu.cn/tex & http://liwzlab.cn/tex) for researchers to further investigate potential association of ICB resistance based on our multi-omics analysis data.

Conclusions

We introduced a novel LUSC immunosuppressive class which expressed high PD-L1 but showed potential resistance to ICB therapy. This comprehensive characterization of immunosuppressive tumour microenvironment in LUSC provided new insights for further exploration of resistance mechanisms and optimization of immunotherapy strategies.
Clinical mobility metrics estimate and characterize physical activity following lower-limb amputation
Authors: Seth Mayank , Pohlig Ryan Todd , Hicks Gregory Evan , Sions Jaclyn Megan
Published: July 2022

Background

Regular physical activity following a lower-limb amputation is essential for maintaining health and a high quality of life. Most adults with a lower-limb amputation, however, participate in insufficient daily physical activity, and thus, are predisposed to poor health outcomes. Estimating physical activity after lower-limb amputation via common mobility metrics may aid in clinical decisions regarding treatment prioritization and prosthesis prescription. The objectives of this study were (a) to examine associations between daily physical activity and patient-reported and performance-based mobility metrics among adults with lower-limb amputation, and (b) to determine whether patient-reported and performance-based mobility metrics can distinguish between physical activity status [i.e., sedentary (< 5000 steps/day) or non-sedentary (≥ 5000 steps/day)] of adults with lower-limb amputation.

Methods

A cross-sectional study involving 35 adults with a unilateral transtibial (N = 23; 63.0 ± 10.4 years) or transfemoral amputation (N = 12; 58.8 ± 9.5 years) was conducted. Participants completed patient-reported (Prosthesis Evaluation Questionnaire-Mobility Subscale) and performance-based mobility metrics (L-Test, 10-m Walk Test, 6-min Walk Test). Physical activity, i.e., average steps/day, was measured with an accelerometer.

Results

Patient-reported and performance-based mobility metrics were associated with daily physical activity (p < 0.050). Prosthesis Evaluation Questionnaire-Mobility Subscale scores, L-Test time, 10-m Walk Test speed and 6-min Walk Test distance independently explained 11.3%, 31.8%, 37.6% and 30.7% of the total variance in physical activity. Receiver operating characteristic curves revealed patient-reported and performance-based mobility metrics significantly distinguish between physical activity status, i.e., sedentary (< 5000 steps/day) versus non-sedentary (≥ 5000 steps/day). Preliminary cut-points for mobility metrics to classify physical activity status were determined.

Conclusions

Following a lower-limb amputation, patient-reported and performance-based mobility metrics may estimate daily physical activity, thereby aiding clinical decisions regarding treatment prioritization as well as prosthesis selection.
Lactobacilli displacement and Candida albicans inhibition on initial adhesion assays: a probiotic analysis
Authors: Rodríguez-Arias Robert Josue , Guachi-Álvarez Bryan Omar , Montalvo-Vivero Dominique Esther , Machado António
Published: July 2022

Objective

This study evaluates the probiotic activity of three vaginalLactobacillus gasseri(H59.2, IMAUFB014, and JCM1131) and one non-vaginalL. plantarumATCC14917 against threeCandida albicans(ATCC10231, candidiasis, and healthy vaginal microbiota). Displacement of lactobacilli and adhesion inhibition ofC. albicanswere evaluated on an abiotic surface through adhesion assays with different experimental settings (ES) through low (1.0E + 03 CFU/ml) and high (1.00E + 09 CFU/ml) levels of colonization. ES simulated dysbiosis (ES1 and ES4), candidiasis (ES2), and healthy vaginal microbiota (ES3).

Results

At ES2 and ES3,L. gasseriH59.2 showed discrepant inhibition values amongC. albicansisolates (ES2:P = 0.008, ES3:P = 0.030; two‐way ANOVA).L. plantarumwas only displaced by 23%, 31%, 54%, and 94% against low and high levels ofC. albicansATCC10231.L. plantarumwas less displaced, when compared toL. gasseristrains (ES1: 61–84%, ES2: 82–96%, ES3: 83–95%, and ES4: 73–97%), showing multiple statistical differences (ES1:P =  < 0.001, ES2:P = 0.003, and ES3:P =  < 0.001; two‐way ANOVA).L. plantarumalso showed a superior inhibition ofC. albicansATCC10231 in ES1 (81%) and ES2 (58%) when compared toL. gasseristrains (ES1: 27–73%,P < 0.001; and ES2:1–49%,P < 0.001; two‐way ANOVA).
AutoClassWeb: a simple web interface for Bayesian clustering of omics data
Authors: Poulain Pierre , Camadro Jean-Michel
Published: July 2022

Objective

Data clustering is a common exploration step in the omics era, notably in genomics and proteomics where many genes or proteins can be quantified from one or more experiments. Bayesian clustering is a powerful unsupervised algorithm that can classify several thousands of genes or proteins. AutoClass C, its original implementation, handles missing data, automatically determines the best number of clusters but is not user-friendly.

Results

We developed an online tool called AutoClassWeb, which provides an easy-to-use and simple web interface for Bayesian clustering with AutoClass. Input data are entered as TSV files and quality controlled. Results are provided in formats that ease further analyses with spreadsheet programs or with programming languages, such as Python or R. AutoClassWeb is implemented in Python and is published under the 3-Clauses BSD license. The source code is available at https://github.com/pierrepo/autoclassweb along with a detailed documentation.
Conditions for uptake of evidence-based knowledge in municipal care for older people in Sweden: a developmental evaluation
Authors: Hultqvist Sara , Ekstam Lisa , Andersson Janicke , Nilsson Maria H. , Overton Marieclaire , Zingmark Magnus , Iwarsson Susanne
Published: July 2022

Objective

The objective of this paper is to describe the initial phase of a long-term collaboration initiative between a municipality and the Faculty of Medicine at a university in Sweden. The overall ambition of the collaboration is to strengthen the quality of care for older people. The concrete goal is to equip academically trained registered health care professionals (HCP) with tools for transferring evidence-based knowledge into practice. As municipal healthcare for older people is mainly carried out by staff lacking academic education, reg. HCP are key actors to bring in and consolidate an evidence-based approach in this setting. Developmental evaluation (DE) has been used to evaluate four separate activities in the initial phase. The activities where sequenced in a cumulative design to provide knowledge for further development of adequate tools.

Results

The cumulative design originally planned did not fit the internal logic of the municipality. Therefore, workflow and pace adjustments were made to proceed towards the joint ambition; the creation of fruitful conditions for the uptake of evidence-based knowledge. Long-term collaboration between academia and organizations outside academia demands a sensitive and flexible research approach, recognizing that collaboration implies mutuality and restricts the sovereignty of academia in designing research.
Chidamide and venetoclax synergistically exert cytotoxicity on multiple myeloma by upregulating BIM expression
Authors: Cao Liqin , Chen Qingxiao , Gu Huiyao , Li Yi , Cao Wen , Liu Yang , Qu Jianwei , Hou Yifan , Chen Jing , Zhang Enfan , He Jingsong , Cai Zhen
Published: July 2022

Background

Multiple myeloma (MM) is the second most common hematologic malignancy with almost all patients eventually having relapse or refractory MM (RRMM), thus novel drugs or combination therapies are needed for improved prognosis. Chidamide and venetoclax, which target histone deacetylase and BCL2, respectively, are two promising agents for the treatment of RRMM.

Results

Herein, we found that chidamide and venetoclax synergistically exert an anti-myeloma effect in vitro in human myeloma cell lines (HMCLs) with a combination index (CI) < 1. Moreover, the synergistic anti-myeloma effect of these two drugs was demonstrated in primary MM cells and MM xenograft mice. Mechanistically, co-exposure to chidamide and venetoclax led to cell cycle arrest at G0/G1 and a sharp increase in DNA double-strand breaks. In addition, the combination of chidamide and venetoclax resulted in BCL-XL downregulation and BIM upregulation, and the latter protein was proved to play a critical role in sensitizing HMCLs to co-treatment.

Conclusion

In conclusion, these results proved the high therapeutic potential of venetoclax and chidamide combination in curing MM, representing a potent and alternative salvage therapy for the treatment of RRMM.
Synthetic MRI in children with tuberous sclerosis complex
Authors: Coban Gokcen , Gumeler Ekim , Parlak Safak , Konuskan Bahadir , Karakaya Jale , Yalnizoglu Dilek , Anlar Banu , Oguz Kader K.
Published: July 2022

Objective

The generation of numerous sequences and quantitative data in a short scanning time is the most potential advantage of Synthetic MRI (SyMRI). We aimed to test detection of the tubers and to determine underlying tissue characteristics, and morphometric alterations in the brain of pediatric tuberous sclerosis complex (TSC) patients, using SyMRI.

Methods

Conventional brain MRI (cMRI) and SyMRI were prospectively obtained from 10 TSC patients and 18 healthy control subjects (HCs). Two neuroradiologists independently evaluated tubers on both scans. Additionally, automatically segmented volume calculation and myelin quantification, including the subcortical part of the tubers and normal-appearing brain parenchyma (NABP) of patients, were carried out using SyMRI.

Results

The cMRI and SyMRI comparison showed a very good correlation on the detection of the tubers (k = 0.82–0.94). Automatic segmentation of Non-gray matter/white matter/cerebrospinal fluid (Non), %Non/brain parenchymal volume, and %Non/intracranial volume was significantly higher; however, %Myelin/intracranial volume and %Myelin/brain parenchymal volume were significantly lower in the TSC patients (p < 0.05). The proton density values were significantly increased, and myelin fraction volume and myelin-correlated compound values were significantly decreased in the NABP in TSC patients on myelin maps (p < 0.05). The white-matter volume, myelin and white-matter fractional volume, longitudinal relaxation rate, transverse relaxation rate, and myelin-correlated compound values were significantly decreased in the subcortical part of tubers on quantification maps (p < 0.001) in TSC patients.

Conclusion

SyMRI enables the detection of cortical tubers and is a developing tool in the quantification of morphometric and tissue alterations in pediatric TSC patients with a rational scanning time.