bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving birth weight measurement and recording practices in Kenya and Tanzania: a prospective intervention study with historical controls
Authors: K’Oloo Alloys , Godfrey Evance , Koivu Annariina M. , Barsosio Hellen C. , Manji Karim , Ndesangia Veneranda , Omiti Fredrick , Khery Mohamed Bakari , Ondieki Everlyne D. , Kariuki Simon , ter Kuile Feiko O. , Chico R. Matthew , Klein Nigel , Heimonen Otto , Ashorn Per , Ashorn Ulla , Näsänen-Gilmore Pieta
Published: May 2023

Background

Low birth weight (LBW) is a significant public health concern given its association with early-life mortality and other adverse health consequences that can impact the entire life cycle. In many countries, accurate estimates of LBW prevalence are lacking due to inaccuracies in collection and gaps in available data. Our study aimed to determine LBW prevalence among facility-born infants in selected areas of Kenya and Tanzania and to assess whether the introduction of an intervention to improve the accuracy of birth weight measurement would result in a meaningfully different estimate of LBW prevalence than current practice.

Methods

We carried out a historically controlled intervention study in 22 health facilities in Kenya and three health facilities in Tanzania. The intervention included: provision of high-quality digital scales, training of nursing staff on accurate birth weight measurement, recording and scale calibration practices, and quality maintenance support that consisted of enhanced supervision and feedback (prospective arm). The historically controlled data were birth weights from the same facilities recorded in maternity registers for the same calendar months from the previous year measured using routine practices and manual scales. We calculated mean birth weight (95% confidence interval CI), mean difference in LBW prevalence, and respective risk ratio (95% CI) between study arms.

Results

Between October 2019 and February 2020, we prospectively collected birth weights from 8441 newborns in Kenya and 4294 in Tanzania. Historical data were available from 9318 newborns in Kenya and 12,007 in Tanzania. In the prospective sample, the prevalence of LBW was 12.6% (95% confidence intervals [CI]: 10.9%–14.4%) in Kenya and 18.2% (12.2%–24.2%) in Tanzania. In the historical sample, the corresponding prevalence estimates were 7.8% (6.5%–9.2%) and 10.0% (8.6%–11.4%). Compared to the retrospective sample, the LBW prevalence in the prospective sample was 4.8% points (3.2%–6.4%) higher in Kenya and 8.2% points (2.3%–14.0%) higher in Tanzania, corresponding to a risk ratio of 1.61 (1.38–1.88) in Kenya and 1.81 (1.30–2.52) in Tanzania.

Conclusion

Routine birth weight records underestimate the risk of LBW among facility-born infants in Kenya and Tanzania. The quality of birth weight data can be improved by a simple intervention consisting of provision of digital scales and supportive training.
Variation of local zoological knowledge about Southern river otter and other semi-aquatic mammals in Nahuel Huapi National Park (Argentina)
Authors: Pozzi Carla M. , Ladio Ana H.
Published: May 2023

Background

The huillín (Lontra provocax, Thomas 1908) is an otter, endemic to southern Argentina and Chile. It is in danger of extinction. In the Nahuel Huapi National Park and surroundings is the only freshwater, known and stable population of huillín in Argentina. In this park, several urban and rural centers coexist with this species. The main objective of our work was to answer: How does the local zoological knowledge (LZK) vary about the huillín, particularly its identification and sighting, among people from different social groups, with different ages and gender, who live in the rural or urban environment and with different periods of permanence in the place?

Methods

Ninety-six written interviews were conducted using visual stimuli to ensure that interviewees refer to the huillín. In addition, we also inquire about the LZK of other species with which it can be confused. Additional open interviews were conducted with participants who observed the huillín to determine the georeferencing of the reported sites and include them on a final map.

Results

95% of people identified the huillín and this was confused with the coipo in 3% and with the american mink, in 5%. The results show that, in general, the LZK did not vary significantly with the sociocultural characteristics of the participants, showing a remarkable homogeneity. However, people in rural areas are more likely to observe the species than people in urban areas. Moreover, people between 20 and 40 years of age are more likely to observe the huillín. The LZK mapping has identified areas that are consistent with and/or adjacent to official source records. Other areas have also been identified that may provide new information.

Conclusion

With this participatory work, we realize that the species is recognized by urban and rural inhabitants and very few confused it. The homogeneity in the LZK found constitutes a kick for the realization of other participatory studies that promote lines of research, action and management that improve the quality of the environments where the only freshwater, known and stable population of the huillín in Argentina lives.
Inclination of mandibular incisors and symphysis in severe skeletal class III malocclusion
Authors: Zhang Jieni , Liang Yuqi , Chen Rui , Chen Si , Lin Jiuxiang , Han Bing , Liu Xiaomo
Published: May 2023

Objective

The aim of this study was to systematically explore the inclination of the lower central incisor and symphysis in alveolar bone in severe skeletal class III patients.

Materials and methods

A total of 198 severe skeletal class III patients (ANB ≤ -4°) who underwent combined orthodontic and orthognathic treatment were divided into three groups based on the mandibular plane angle (MP-SN). Pretreatment lateral cephalograms were analysed and compared among the three groups. We also assessed cone-beam computed tomography (CBCT) images of 11 samples to investigate the reliability of the cephalometric analysis.

Results

ANOVA showed no statistically significant differences in the angle between the long axis of the mandibular symphysis and the long axis of the lower central incisor (MIA) among the low-angle, normal-angle and high-angle groups (P > 0.05), while significant differences were found in the angle between the axis of the lower incisor and the mandibular plane (IMPA) among the three groups (P < 0.001). The mean IMPA decreased with increasing MP-SN in the 198 patients. The mean MIA in the low-angle and normal-angle groups was 3.70° and 3.52°, respectively, while the value (2.33°) was smaller in the high-angle group. Paired-samples t test showed no statistically significant differences between the cephalometric and CBCT measurements of the MP-SN, the angle between the mandibular plane and the Frankfort plane (FH-MP) and the MIA (P > 0.05).

Conclusions

In severe skeletal class III patients, the long axis of the lower central incisor was highly consistent with the long axis of the mandibular symphysis, which was more obvious in the high-angle subjects. The MIA reflects the physiological inclination of the lower central incisor better than the IMPA.
The effect of type 2 diabetes mellitus on the prognosis of osteoporotic vertebral compression fracture with osteoporotic fracture classification after vertebroplasty
Authors: Wang Zixiang , Wang Hanquan , Zhuang Chenyang , Chen Weisin , Hoang Tien-Manh , Li Juan , Lin Hong
Published: May 2023

Background

To analyze the clinical and radiological effects of type 2 diabetes mellitus on the prognosis of osteoporotic vertebral compression fracture after percutaneous vertebroplasty, and explore the prognostic value of osteoporotic fracture classification.

Methods

Osteoporotic vertebral compression fracture patients who received vertebroplasty from January 1, 2016 to June 30, 2021 were divided into type 2 diabetes mellitus group and control group in this retrospective cohort study. Visual analogue scale, Oswestry Disability Index, bone cement leakage, new compression fracture, anterior, middle, and posterior portion heights of vertebral body and local Cobb angle on X-ray before surgery, 2 days after surgery, 6 months, and 12 months after surgery were recorded, and the osteoporotic fracture classification was performed. P < 0.05 was set as statistical significance.

Results

A total of 261 vertebral bodies were included, containing 68 in the type 2 diabetes mellitus group and 193 in the control group. There were no differences in baseline characteristics between the two groups. At 6 months after vertebroplasty, the local Cobb angle of the type 2 diabetes mellitus group was 8.29 ± 4.90° greater than that of the control group 6.05 ± 5.18° (P = 0.002). At 12 months, compared with pre-operation, the anterior portion height recovered 8.13 ± 12.90%, which was less than 12.51 ± 14.92% of the control group (P = 0.032), and 19.07 ± 16.47% of the middle portion height recovery was less than the control group’s 24.63 ± 17.67% (P = 0.024). Compared with the control group, osteoporotic fracture 2 vertebral bodies of the type 2 diabetes mellitus group at 12 months postoperatively in middle portion height (14.82 ± 14.71% vs 24.78 ± 18.16%, P = 0.023) and local Cobb angle (5.65 ± 4.06° vs 3.26 ± 4.86°, P = 0.043) restored significantly worse. Besides, osteoporotic fracture 3 with type 2 diabetes mellitus restored worse in anterior portion height (5.40 ± 11.02% vs 13.57 ± 12.79%, P = 0.008), middle portion height (11.22 ± 15.53% vs 17.84 ± 12.36%, P = 0.041) and local Cobb angle (10.85 ± 3.79 vs 7.97 ± 3.83°, P = 0.002) at 12 months postoperatively. There was no difference in radiological outcomes of osteoporotic fracture 4 between the two groups.

Conclusions

The degree of fractured vertebral compression, the recovery of the height and angle obtained immediately after surgery and the clinical symptoms in type 2 diabetes mellitus patients were not different from those in the control. However, vertebral body morphology of type 2 diabetes mellitus patients was worse since the sixth month after surgery. Osteoporotic fracture classification has a good prognostic reference value for both the control and the type 2 diabetes mellitus population.
Risk factors for perioperative acute heart failure in older hip fracture patients and establishment of a nomogram predictive model
Authors: Tian Miao , Li Wenjing , Wang Yan , Tian Yunxu , Zhang Kexin , Li Xiuting , Zhu Yanbin
Published: May 2023

Aim

This study aims to explore the risk factors for perioperative acute heart failure in older patients with hip fracture and establish a nomogram prediction model.

Methods

The present study was a retrospective study. From January 2020 to December 2021, patients who underwent surgical treatment for hip fracture at the Third Hospital of Hebei Medical University were included. Heart failure was confirmed by discharge diagnosis or medical records. The samples were randomly divided into modeling and validation cohorts in a ratio of 7:3. Relevant demographic and clinic data of patients were collected. IBM SPSS Statistics 26.0 performed univariate and multivariate logistic regression analysis, to obtain the risk factors of acute heart failure. The R software was used to construct the nomogram prediction model.

Results

A total of 751 older patients with hip fracture were enrolled in this study, of which 138 patients (18.37%, 138/751) developed acute heart failure. Heart failure was confirmed by discharge diagnosis or medical records. Respiratory disease (odd ratio 7.68; 95% confidence interval 3.82–15.43; value of P 0.001), history of heart disease (chronic heart failure excluded) (odd ratio 2.21, 95% confidence interval 1.18–4.12; value of P 0.010), ASA ≥ 3 (odd ratio 14.46, 95% confidence interval 7.78–26.87; value of P 0.001), and preoperative waiting time ≤ 2 days (odd ratio 3.32, 95% confidence interval 1.33–8.30; value of P 0.010) were independent risk factors of perioperative acute heart failure in older patients with hip fracture. The area under the curve (AUC) of the prediction model based on these factors was calculated to be 0.877 (95% confidence interval 0.836–0.918). The sensitivity and specificity were 82.8% and 80.9%, respectively, and the fitting degree of the model was good. In the internal validation group, the AUC was 0.910, and the 95% confidence interval was 0.869–0.950.

Conclusions

Several risk factors are identified for acute heart failure in older patients, based on which pragmatic nomogram prediction model is developed, facilitating detection of patients at risk early.
Using WeChat to guide preparation before transthoracic echocardiography reduces anxiety and improves satisfaction of parents of infants with congenital heart disease
Authors: Guo Shan , Lin Wen-Hao , Lin Shi-Hao , Zhang Qi-Liang , Cao Hua , Chen Qiang
Published: May 2023

Objective

To explore the effect of using WeChat to guide preparation before transthoracic echocardiography (TTE) on reducing anxiety and improving the satisfaction of parents of infants with congenital heart disease (CHD).

Methods

This study was a retrospective study conducted in a children’s hospital. The clinical data of 44 patients and the anxiety and satisfaction data of their parents who received WeChat guidance were collected between December 2021 and January 2022 (the WeChat group). The corresponding data of 47 patients and their parents who received educational brochure guidance were collected between September 2021 and November 2021 (the routine group). Guidance was used to help the parents prepare for TTE performed by medical professionals. The State-Trait Anxiety Inventory scale and the Patient Satisfaction Questionnaire-18 (PSQ-18) were used. The data of the two groups were compared and analyzed.

Results

The comparison of parental anxiety between the two groups showed that the scores of state anxiety and trait anxiety in the WeChat group were significantly lower than those in the routine group (p < 0.05). The comparison of the results of the PSQ-18 showed that the scores for general satisfaction, interpersonal manner, communication, time spent with the physician, and accessibility and convenience in the WeChat group were significantly higher than those in the routine group (p < 0.05).

Conclusion

Using WeChat to guide preparation before TTE for infants with CHD can effectively reduce the anxiety of their parents and improve their parents’ satisfaction with medical treatment.
Identification of a novel de novo mutation of SETBP1 and new findings of SETBP1 in tumorgenesis
Authors: Wang Hongdan , Gao Yue , Qin Litao , Zhang Mengting , Shi Weili , Feng Zhanqi , Guo Liangjie , Zhu Bofeng , Liao Shixiu
Published: May 2023

Background

In the past decade, SETBP1 has attracted a lot of interest on that the same gene with different type or level (germline or somatic) of variants could provoke different pathologic consequences such as Schinzel-Giedon syndrome, SETBP1 Haploinsufficiency Disorder (SETBP1-HD) and myeloid malignancies. Whole exome sequencing was conducted to detect the etiology of a pregnant woman with mental retardation. As a new oncogene and potential marker of myeloid malignancies, somatic SETBP1 variants in other cancers were rarely studied. We performed a pan-cancer analysis of SETBP1 gene in different cancers for the first time.

Results

A novel heterozygous mutation of the SETBP1 gene (c.1724_1727del, p.D575Vfs*4) was found in the patient and the fetus and the mutation was predicted to result in a truncated protein. Reduced SETBP1 expression was associated with SETBP1-HD. The pan-cancer analysis of SETBP1 showed that SETBP1 overexpression should be given special attention in Bladder Urothelial Carcinoma (BLCA) and Stomach adenocarcinoma (STAD).

Conclusions

The de novo SETBP1 mutation was the genetic cause of SETBP1-HD in the family. BLCA and STAD might be related to SETBP1 overexpression.
Practices and challenges for hemophilia management under resource constraints in Thailand
Authors: Moonla Chatphatai , Sosothikul Darintr , Pongtanakul Bunchoo , Suwanawiboon Bundarika , Traivaree Chanchai , Natesirinilkul Rungrote , Sirachainan Nongnuch , Angchaisuksiri Pantep
Published: May 2023

Hemophilia is an inherited bleeding disorder caused by deficiency of a specific coagulation factor. Factor VIII deficiency is responsible for hemophilia A while factor IX deficiency is responsible for hemophilia B. As per the 2020 annual global survey by the World Federation of Hemophilia, only 1828 Thai hemophiliacs have been registered to the national healthcare system. The reason for the low number is the underdiagnosis which is a major concern in the real-world practice among Asian countries. In Thailand, most hemophiliacs are diagnosed by general practitioners, pediatricians or internists at rural hospitals and are referred to hemophilia specialists at the Hemophilia Treatment Centers (HTCs). Despite the challenges pertaining to infrastructure and cost of treatment, Thailand has progressed substantially in providing the required hemophilia care, as evidenced by an evolution in acquiring and sharing knowledge as well as collaborative efforts among multiple stakeholders over the past three decades. In this letter-to-the-editor, the authors have summarized the practices for and challenges faced with hemophilia management in Thailand.
Area level indirect exposure to extended conflicts and early childhood anthropometric outcomes in India: a repeat cross-sectional analysis
Authors: Chatterjee Pritha , Chen Jarvis , Yousafzai Aisha , Kawachi Ichiro , Subramanian S. V.
Published: May 2023

Background

Protracted, internal conflicts with geographic variations within countries, are an important understudied community exposure for adverse child health outcomes.

Methods

Violent events from the Uppsala Conflict Data Program (UCDP) between January 2016–December 2020 and January 2010–December 2015, were included as exposure events for children sampled in National Family Health Surveys (NFHS) 5 (2019–21) and NFHS 4 (2015–16), respectively. Geocoded data from UCDP were merged with residential clusters from NFHS, to identify children living in villages or urban blocks situated at <= 50 km from conflict sites. Within these clusters, which we defined as conflict exposed, we studied risks of stunting, underweight and wasting in children, prenatally, and in 0–3 years. We assessed sensitivity on a subsample of siblings with discordant conflict exposures.

Results

For NFHS 5, exposure to violence between 0 and 3 years was associated with 1.16 times (95% CI 1.11–1.20) higher risks of stunting, 1.08 (1.04, 1.12) times higher risks of underweight, and no change in wasting. In-utero violence exposure was associated with 1.11 times (95% CI 1.04–1.17) higher risks of stunting, 1.08 (95% CI 1.02–1.14) times higher risks of underweight, and no change in wasting, among children <= 2 years. In 17,760 siblings of 8333 mothers, exposure to violence during 0–3 years, was associated with a 1.19 times higher risk of stunting (95% CI − 0.24 to 0.084). Incremental quartiles of violence exposure had higher risks of stunting and underweight until quartile 3.

Conclusion

In-utero and early childhood indirect exposure to protracted conflicts were associated with increased stunting and underweight in India. Given the continued exposures of such historically and contextually rooted internal conflicts in many LMICs, chronic violence exposures should be targeted in public health policies as important social and political determinant of child health.
Piperlongumine conquers temozolomide chemoradiotherapy resistance to achieve immune cure in refractory glioblastoma via boosting oxidative stress-inflamation-CD8+-T cell immunity
Authors: Liu Feng , Zhou Qian , Jiang Hai-feng , Zhang Ting-ting , Miao Cheng , Xu Xiao-hong , Wu Jia-xing , Yin Song-lin , Xu Shi-jie , Peng Jing-yi , Gao Pan-pan , Cao Xuan , Pan Feng , He Ximiao , Chen Xiao Qian
Published: May 2023

Background

The failure of novel therapies effective in preclinical animal models largely reflects the fact that current models do not really mimic the pathological/therapeutic features of glioblastoma (GBM), in which the most effective temozolomide chemoradiotherapy (RT/TMZ) regimen can only slightly extend survival. How to improve RT/TMZ efficacy remains a major challenge in clinic.

Methods

Syngeneic G422TN-GBM model mice were subject to RT/TMZ, surgery, piperlongumine (PL), αPD1, glutathione. Metabolomics or transcriptomics data from G422TN-GBM and human GBM were used for gene enrichment analysis and estimation of ROS generation/scavenging balance, oxidative stress damage, inflammation and immune cell infiltration. Overall survival, bioluminescent imaging, immunohistochemistry, and immunofluorescence staining were used to examine therapeutic efficacy and mechanisms of action.

Results

Here we identified that glutathione metabolism was most significantly altered in metabolomics analysis upon RT/TMZ therapies in a truly refractory and reliable mouse triple-negative GBM (G422TN) preclinical model. Consistently, ROS generators/scavengers were highly dysregulated in both G422TN-tumor and human GBM. The ROS-inducer PL synergized surgery/TMZ, surgery/RT/TMZ or RT/TMZ to achieve long-term survival (LTS) in G422TN-mice, but only one LTS-mouse from RT/TMZ/PL therapy passed the rechallenging phase (immune cure). Furthermore, the immunotherapy of RT/TMZ/PL plus anti-PD-1 antibody (αPD1) doubled LTS (50%) and immune-cured (25%) mice. Glutathione completely abolished PL-synergistic effects. Mechanistically, ROS reduction was associated with RT/TMZ-resistance. PL restored ROS level (mainly via reversing Duox2/Gpx2), activated oxidative stress/inflammation/immune responses signature genes, reduced cancer cell proliferation/invasion, increased apoptosis and CD3+/CD4+/CD8+ T-lymphocytes in G422TN-tumor on the basis of RT/TMZ regimen.

Conclusion

Our findings demonstrate that PL reverses RT/TMZ-reduced ROS and synergistically resets tumor microenvironment to cure GBM. RT/TMZ/PL or RT/TMZ/PL/αPD1 exacts effective immune cure in refractory GBM, deserving a priority for clinical trials.
Genome-wide association analysis reveals a novel pathway mediated by a dual-TIR domain protein for pathogen resistance in cotton
Authors: Zhang Yihao , Zhang Yaning , Ge Xiaoyang , Yuan Yuan , Jin Yuying , Wang Ye , Zhao Lihong , Han Xiao , Hu Wei , Yang Lan , Gao Chenxu , Wei Xi , Li Fuguang , Yang Zhaoen
Published: May 2023

Background

Verticillium wilt is one of the most devasting diseases for many plants, leading to global economic loss. Cotton is known to be vulnerable to its fungal pathogen, Verticillium dahliae, yet the related genetic mechanism remains unknown.

Results

By genome-wide association studies of 419 accessions of the upland cotton, Gossypium hirsutum, we identify ten loci that are associated with resistance against Verticillium wilt. Among these loci, SHZDI1/SHZDP2/AYDP1 from chromosome A10 is located on a fragment introgressed from Gossypium arboreum. We characterize a large cluster of Toll/interleukin 1 (TIR) nucleotide-binding leucine-rich repeat receptors in this fragment. We then identify a dual-TIR domain gene from this cluster, GhRVD1, which triggers an effector-independent cell death and is induced by Verticillium dahliae. We confirm that GhRVD1 is one of the causal gene for SHZDI1. Allelic variation in the TIR domain attenuates GhRVD1-mediated resistance against Verticillium dahliae. Homodimerization between TIR1-TIR2 mediates rapid immune response, while disruption of its αD- and αE-helices interface eliminates the autoactivity and self-association of TIR1-TIR2. We further demonstrate that GhTIRP1 inhibits the autoactivity and self-association of TIR1-TIR2 by competing for binding to them, thereby preventing the resistance to Verticillium dahliae.

Conclusions

We propose the first working model for TIRP1 involved self-association and autoactivity of dual-TIR domain proteins that confer compromised pathogen resistance of dual-TIR domain proteins in plants. The findings reveal a novel mechanism on Verticillium dahliae resistance and provide genetic basis for breeding in future.
Effectiveness of motor control exercise, aerobic walking, and muscle strengthening programs in improving outcomes in a subgroup of population with chronic low back pain positive for central sensitization: a study protocol for a randomized controlled trial
Authors: Ganesh G. Shankar , Khan Abdur Raheem , Das Sakti Prasad , Khan Ashfaque , Alqhtani Raee S. , Alshahrani Adel , Jarrar Mohammad Abdulrehman Mohammad , Ahmed Hashim
Published: May 2023

Background

The role of pain sensitivity in the development and maintenance of chronic pain states, impaired executive functioning, and patient recovery is being investigated. Conditioned pain modulation (CPM) is widely used to measure musculoskeletal pain associated with central sensitization (CS). Despite the recommendations of many reviews and clinical practice guidelines that exercise programs reduce pain and disability, the overall confidence in these results is considered “critically low.” The “active ingredient” of exercise programs and the dominant factor influencing CPM remain largely unknown.

The objectives of this trial are to determine:

• If different exercises cause different results on the CPM in a subgroup of people with chronic low back pain (CLBP) who are labeled as having CS pain,

• If a program of exercise interventions for 12 weeks would alter executive functioning, quality of life (QoL), disability, and pain in persons with CLBP.

• The relationship between patient characteristics, executive functions, CPM, and QoL

Methods

The trial is a randomized, controlled, multi-center study with four experimental groups and one healthy control group. Both the researchers and the people in the study will be blinded to the results. This paper describes the protocol for a trial examining the effects of 12-week individualized, twice-weekly exercise sessions lasting 30 to 60 min in persons with CLBP, who are positive for CS. Participants will be randomized to receive either patient education with motor control exercises (MCE), superficial strengthening (SS), aerobic exercises (AE), or patient education alone. Another group comprised of healthy volunteers will serve as controls. The primary outcomes are changes in CPM outcomes as measured by the cold pressor test (CPT). The secondary objectives are to evaluate executive functioning, pain, disability, quality of life, and spine muscle strength. The outcomes will be measured at 3 months and at a 6-month follow-up.

Discussion

The outcomes of the study will help in gaining more information and evidence about exercise-induced analgesia from the perspective of CPM. Measuring exercise outcomes will aid in scientifically prescribing exercise prescriptions in people with CLBP. The study outcomes will also assist in identifying the characteristics of individuals who will respond or respond indifferently to exercises. Investigating the relationship between the study’s various outcomes could provide information for future trials.

Trial registration

Clinical Trials Registry of India (CTRI) identifier: CTRI/2022/03/041143. Registered on 16 March 2022.
High level of complexity and global diversity of the 3q29 locus revealed by optical mapping and long-read sequencing
Authors: Yilmaz Feyza , Gurusamy Umamaheswaran , Mosley Trenell J. , Hallast Pille , Kim Kwondo , Mostovoy Yulia , Purcell Ryan H. , Shaikh Tamim H. , Zwick Michael E. , Kwok Pui-Yan , Lee Charles , Mulle Jennifer G.
Published: May 2023

Background

High sequence identity between segmental duplications (SDs) can facilitate copy number variants (CNVs) via non-allelic homologous recombination (NAHR). These CNVs are one of the fundamental causes of genomic disorders such as the 3q29 deletion syndrome (del3q29S). There are 21 protein-coding genes lost or gained as a result of such recurrent 1.6-Mbp deletions or duplications, respectively, in the 3q29 locus. While NAHR plays a role in CNV occurrence, the factors that increase the risk of NAHR at this particular locus are not well understood.

Methods

We employed an optical genome mapping technique to characterize the 3q29 locus in 161 unaffected individuals, 16 probands with del3q29S and their parents, and 2 probands with the 3q29 duplication syndrome (dup3q29S). Long-read sequencing-based haplotype resolved de novo assemblies from 44 unaffected individuals, and 1 trio was used for orthogonal validation of haplotypes and deletion breakpoints.

Results

In total, we discovered 34 haplotypes, of which 19 were novel haplotypes. Among these 19 novel haplotypes, 18 were detected in unaffected individuals, while 1 novel haplotype was detected on the parent-of-origin chromosome of a proband with the del3q29S. Phased assemblies from 44 unaffected individuals enabled the orthogonal validation of 20 haplotypes. In 89% (16/18) of the probands, breakpoints were confined to paralogous copies of a 20-kbp segment within the 3q29 SDs. In one del3q29S proband, the breakpoint was confined to a 374-bp region using long-read sequencing. Furthermore, we categorized del3q29S cases into three classes and dup3q29S cases into two classes based on breakpoints. Finally, we found no evidence of inversions in parent-of-origin chromosomes.

Conclusions

We have generated the most comprehensive haplotype map for the 3q29 locus using unaffected individuals, probands with del3q29S or dup3q29S, and available parents, and also determined the deletion breakpoint to be within a 374-bp region in one proband with del3q29S. These results should provide a better understanding of the underlying genetic architecture that contributes to the etiology of del3q29S and dup3q29S.
Sex differences in the polygenic architecture of hearing problems in adults
Authors: De Angelis Flavio , Zeleznik Oana A. , Wendt Frank R. , Pathak Gita A. , Tylee Daniel S. , De Lillo Antonella , Koller Dora , Cabrera-Mendoza Brenda , Clifford Royce E. , Maihofer Adam X. , Nievergelt Caroline M. , Curhan Gary C. , Curhan Sharon G. , Polimanti Renato
Published: May 2023

Background

Hearing problems (HP) in adults are common and are associated with several comorbid conditions. Its prevalence increases with age, reflecting the cumulative effect of environmental factors and genetic predisposition. Although several risk loci have been already identified, HP biology and epidemiology are still insufficiently investigated by large-scale genetic studies.

Methods

Leveraging the UK Biobank, the Nurses’ Health Studies (I and II), the Health Professionals Follow-up Study, and the Million Veteran Program, we conducted a comprehensive genome-wide investigation of HP in 748,668 adult participants (discovery N = 501,825; replication N = 226,043; cross-ancestry replication N = 20,800). We leveraged the GWAS findings to characterize HP polygenic architecture, exploring sex differences, polygenic risk across ancestries, tissue-specific transcriptomic regulation, cause-effect relationships with genetically correlated traits, and gene interactions with HP environmental risk factors.

Results

We identified 54 risk loci and demonstrated that HP polygenic risk is shared across ancestry groups. Our transcriptomic regulation analysis highlighted the potential role of the central nervous system in HP pathogenesis. The sex-stratified analyses showed several additional associations related to peripheral hormonally regulated tissues reflecting a potential role of estrogen in hearing function. This evidence was supported by the multivariate interaction analysis that showed how genes involved in brain development interact with sex, noise pollution, and tobacco smoking in relation to their HP associations. Additionally, the genetically informed causal inference analysis showed that HP is linked to many physical and mental health outcomes.

Conclusions

The results provide many novel insights into the biology and epidemiology of HP in adults. Our sex-specific analyses and transcriptomic associations highlighted molecular pathways that may be targeted for drug development or repurposing. Additionally, the potential causal relationships identified may support novel preventive screening programs to identify individuals at risk.
CRISPR-Cas9 knockout screen identifies novel treatment targets in childhood high-grade glioma
Authors: Wenger Anna , Karlsson Ida , Kling Teresia , Carén Helena
Published: May 2023

Background

Brain tumours are the leading cause of cancer-related death in children, and there is no effective treatment. A growing body of evidence points to deregulated epigenetics as a tumour driver, particularly in paediatric cancers as they have relatively few genomic alterations, and key driver mutations have been identified in histone 3 (H3). Cancer stem cells (CSC) are implicated in tumour development, relapse and therapy resistance and thus particularly important to target. We therefore aimed to identify novel epigenetic treatment targets in CSC derived from H3-mutated high-grade glioma (HGG) through a CRISPR-Cas9 knockout screen.

Results

The knockout screen identified more than 100 novel genes essential for the growth of CSC derived from paediatric HGG with H3K27M mutation. We successfully validated 12 of the 13 selected hits by individual knockout in the same two CSC lines, and for the top six hits we included two additional CSC lines derived from H3 wild-type paediatric HGG. Knockout of these genes led to a significant decrease in CSC growth, and altered stem cell and differentiation markers.

Conclusions

The screen robustly identified essential genes known in the literature, but also many novel genes essential for CSC growth in paediatric HGG. Six of the novel genes (UBE2N, CHD4,LSM11, KANSL1, KANSL3andEED)were validated individually thus demonstrating their importance for CSC growth in H3-mutated and wild-type HGG. These genes should be further studied and evaluated as novel treatment targets in paediatric HGG.
Granuloma annulare with alopecia areata in a 6-year-old girl: a case report
Authors: Mohaghegh Fatemeh , Moeine Reza , Saber Mina , Fatemeh Safdarian , Nekooeian Mohammad , Shahriarirad Reza
Published: May 2023

Background

Dermatologic signs and symptoms can be the manifestations of a single disease or different diseases, and it is proven that some are associated with one another. These connections are not fully understood, but the answer lies in the pathophysiology of each disease.

Case presentation

We report the case of a 6-year-old Middle-Eastern girl who presented with two skin lesions on the dorsum of her foot, along with scaling of her soles and palms, face skin discoloration, and areas of patchy alopecia on her scalp. She was diagnosed as a case of acute onset of granuloma annulare with alopecia areata and dermatitis. The treatment regimen for the patient’s scalp consisted of topical minoxidil and betamethasone and three sessions with 1-month intervals of triamcinolone acetonide intralesional injections, which demonstrated modest effectiveness in treating alopecia areata.

Conclusion

Granuloma annulare is a benign inflammatory illness with no known cause that might be difficult to cure. The clinical course and prognosis might vary greatly depending on the disease subtype, and associating symptoms and diseases, such as alopecia areata, should be considered.
Anomalous aortic origin of right coronary artery from left coronary cusp: a management conundrum: a case report
Authors: Arun Kumar Pramukh , Patel Boskey , Dasari Mahati , Bhattad Pradnya Brijmohan , Prabhu Sushmita , Hadley Michelle
Published: May 2023

Background

Coronary artery anomalies are characterized by an abnormality in the course or origin of three main coronary arteries. There needs to be more scientific evidence to promptly treat coronary artery anomalies with poorly understood prognostic implications, especially anomalous aortic origin of the right coronary artery from the left coronary cusp.

Case presentation

A 58-year-old Caucasian female presented multiple times over 6 months with atypical chest discomfort and palpitations. The treadmill exercise test demonstrated exercise-induced non-sustained ventricular tachycardia. A coronary angiogram revealed no obstructive coronary artery disease and an anomalous aortic origin of the right coronary artery from the left coronary cusp with an interarterial course. She was managed conservatively with medications, despite persistent recurrent symptoms.

Conclusion

It is essential to identify subtle symptoms and insidious onset of anomalous aortic origin of the right coronary artery symptoms as seen in our patient, which can contribute to significant morbidity. There are discrepancies in existing guidelines between different cardiovascular societies in managing selected subgroups of patients with anomalous aortic origin of the right coronary artery who do not have high-risk features, but continue to remain symptomatic.
Unexpected presentation of accessory breast: vulvar accessory breast tissue: a case report
Authors: Mansouri Ghazal , Alkatout Ibrahim , Iranpour Maryam , Pourkhandani Elham , Allahqoli Leila
Published: May 2023

Background

The accessory breast is composed of residual glandular mammary tissue that persists after normal embryonic development. The entity is so rare that it is easily neglected in the diagnosis of disease.

Case presentation

We report a 24-year-old virgin Persian woman with a left-sided vulvar mass and no pain or discomfort until shortly before her presentation at our department. Ectopic breast tissue in the vulva was diagnosed. We performed wide local resection of the lesion. Pathological investigation of the lesion confirmed the presence of ectopic breast tissue with secretory changes. She had no specific developmental abnormalities and had no relevant family history. She was followed up for 10 months and had recovered fully by this time.

Conclusion

Accessory breast tissue should be considered as a diagnosis when a mass is seen along the embryonic milk line, especially if the clinical findings reveal changes in the mass accompanied by changes in sex hormones.
NAD+ metabolism-based immunoregulation and therapeutic potential
Authors: Fang Jiankai , Chen Wangwang , Hou Pengbo , Liu Zhanhong , Zuo Muqiu , Liu Shisong , Feng Chao , Han Yuyi , Li Peishan , Shi Yufang , Shao Changshun
Published: May 2023

Nicotinamide adenine dinucleotide (NAD+) is a critical metabolite that acts as a cofactor in energy metabolism, and serves as a cosubstrate for non-redox NAD+-dependent enzymes, including sirtuins, CD38 and poly(ADP-ribose) polymerases. NAD+metabolism can regulate functionality attributes of innate and adaptive immune cells and contribute to inflammatory responses. Thus, the manipulation of NAD+bioavailability can reshape the courses of immunological diseases. Here, we review the basics of NAD+biochemistry and its roles in the immune response, and discuss current challenges and the future translational potential of NAD+research in the development of therapeutics for inflammatory diseases, such as COVID-19.
Health promotion and disease prevention registries in the EU: a cross country comparison
Authors: Rossmann Christin , Krnel Sandra Radoš , Kylänen Marika , Lewtak Katarzyna , Tortone Claudio , Ragazzoni Paola , Grasso Mara , Maassen Alison , Costa Luciana , van Dale Djoeke
Published: May 2023

Background

Health promotion and disease prevention programme registries (HPPRs), also called ‘best practice portals’, serve as entry points and practical repositories that provide decision-makers with easy access to (evidence-based) practices. However, there is limited knowledge of differences or overlaps of howe current national HPPRs in Europe function, the context and circumstances in which these HPPRs were developed, and the mechanisms utilised by each HPPR for the assessment, classification and quality improvement of the included practices. This study prepared an overview of different approaches in several national HPPRs and the EU Best Practice Portal (EU BPP) as well as identified commonalities and differences among the core characteristics of the HPPRs.

Methods

We conducted a descriptive comparison – that focused on six European countries with existing or recently developed/implemented national HPPR and the EU BPP –to create a comparative overview. We used coding mechanisms to identify commonalities and differences; we performed data management, collection and building consensus during EuroHealthNet Thematic Working Group meetings.

Results

All HPPRs offer a broad range of health promotion and disease-prevention practices and serve to support practitioners, policymakers and researchers in selecting practices. Almost all HPPRs have an assessment process in place or planned, requiring the application of assessment criteria that differ among the HPPRs. While all HPPRs collect and share recommendable practices, others have implemented further measures to improve the quality of the submitted practices. Different dissemination tools and strategies are employed to promote the use of the HPPRs, including social media, newsletters and publications as well as capacity building workshops for practice owners or technical options to connect citizens/patients with local practices.

Conclusions

Collaboration between HPPRs (at national and EU level) is appreciated, especially regarding the use consistent terminology to avoid misinterpretation, facilitate cross-country comparison and enable discussions on the adaption of assessment criteria by national HPPRs. Greater efforts are needed to promote the actual implementation and transfer of practices at the national level to address public health challenges with proven and effective practices.
Improving alcohol health literacy and reducing alcohol consumption: recommendations for Germany
Authors: Manthey Jakob , Kokole Daša , Riedel-Heller Steffi , Rowlands Gill , Schäfer Ingo , Schomerus Georg , Soellner Renate , Kilian Carolin
Published: May 2023

Background

Although the detrimental health effects of alcohol are well established, consumption levels are high in many high-income countries such as Germany. Improving alcohol health literacy presents an integrated approach to alcohol prevention and an important complement to alcohol policy. Our aim was to identify and prioritize measures to enhance alcohol health literacy and hence to reduce alcohol consumption, using Germany as an example.

Methods

A series of recommendations for improving alcohol health literacy were derived from a review of the literature and subsequently rated by five experts. Recommendations were rated according to their likely impact on enhancing (a) alcohol health literacy and (b) reducing alcohol consumption. Inter-rater agreement was assessed using a two-way intra-class correlation coefficient (ICC).

Results

Eleven recommendations were established for three areas of action: (1) education and information, (2) health care system, and (3) alcohol control policy. Education and information measures were rated high to increase alcohol health literacy but low to their impact on alcohol consumption, while this pattern was reversed for alcohol control policies. The ratings showed good agreement (ICC: 0.85–0.88).

Conclusions

Improving alcohol health literacy and reducing alcohol consumption should be considered complementary and become part of a comprehensive alcohol strategy to curb the health, social, and economic burden of alcohol.
Improving the accuracy of genomic prediction for meat quality traits using whole genome sequence data in pigs
Authors: Zhuang Zhanwei , Wu Jie , Qiu Yibin , Ruan Donglin , Ding Rongrong , Xu Cineng , Zhou Shenping , Zhang Yuling , Liu Yiyi , Ma Fucai , Yang Jifei , Sun Ying , Zheng Enqin , Yang Ming , Cai Gengyuan , Yang Jie , Wu Zhenfang
Published: May 2023

Background

Pork quality can directly affect customer purchase tendency and meat quality traits have become valuable in modern pork production. However, genetic improvement has been slow due to high phenotyping costs. In this study, whole genome sequence (WGS) data was used to evaluate the prediction accuracy of genomic best linear unbiased prediction (GBLUP) for meat quality in large-scale crossbred commercial pigs.

Results

We produced WGS data (18,695,907 SNPs and 2,106,902 INDELs exceed quality control) from 1,469 sequenced Duroc × (Landrace × Yorkshire) pigs and developed a reference panel for meat quality including meat color score, marbling score, L* (lightness), a* (redness), and b* (yellowness) of genomic prediction. The prediction accuracy was defined as the Pearson correlation coefficient between adjusted phenotypes and genomic estimated breeding values in the validation population. Using different marker density panels derived from WGS data, accuracy differed substantially among meat quality traits, varied from 0.08 to 0.47. Results showed that MultiBLUP outperform GBLUP and yielded accuracy increases ranging from 17.39% to 75%. We optimized the marker density and found medium- and high-density marker panels are beneficial for the estimation of heritability for meat quality. Moreover, we conducted genotype imputation from 50K chip to WGS level in the same population and found average concordance rate to exceed 95% and r2 = 0.81.

Conclusions

Overall, estimation of heritability for meat quality traits can benefit from the use of WGS data. This study showed the superiority of using WGS data to genetically improve pork quality in genomic prediction.
From threat to challenge—Improving medical students’ stress response and communication skills performance through the combination of stress arousal reappraisal and preparatory worked example-based learning when breaking bad news to simulated patients: study protocol for a randomized controlled trial
Authors: Bosshard Michel , Schmitz Felix Michael , Guttormsen Sissel , Nater Urs Markus , Gomez Patrick , Berendonk Christoph
Published: May 2023

Background

Breaking bad news (BBN; e.g., delivering a cancer diagnosis) is perceived as one of the most demanding communication tasks in the medical field and associated with high levels of stress. Physicians’ increased stress in BBN encounters can negatively impact their communication performance, and in the long term, patient-related health outcomes. Although a growing body of literature acknowledges the stressful nature of BBN, little has been done to address this issue. Therefore, there is a need for appropriate tools to help physicians cope with their stress response, so that they can perform BBN at their best. In the present study, we implement the biopsychosocial model of challenge and threat as theoretical framework. According to this model, the balance between perceived situational demands and perceived coping resources determines whether a stressful performance situation, such as BBN, is experienced as challenge (resources > demands) or threat (resources < demands). Using two interventions, we aim to support medical students in shifting towards challenge-oriented stress responses and improved communication performance: (1) stress arousal reappraisal (SAR), which guides individuals to reinterpret their stress arousal as an adaptive and beneficial response for task performance; (2) worked examples (WE), which demonstrate how to BBN in a step-by-step manner, offering structure and promoting skill acquisition.

Methods

In a randomized controlled trial with a 2 (SAR vs. control) x 2 (WE vs. control) between-subjects design, we will determine the effects of both interventions on stress response and BBN skills performance in N = 200 third-year medical students during a simulated BBN encounter. To identify students’ stress responses, we will assess their perceived coping resources and task demands, record their cardiovascular activity, and measure salivary parameters before, during, and after BBN encounters. Three trained raters will independently score students’ BBN skills performances.

Discussion

Findings will provide unique insights into the psychophysiology of medical students who are tasked with BBN. Parameters can be understood more comprehensively from the challenge and threat perspective and linked to performance outcomes. If proven effective, the evaluated interventions could be incorporated into the curriculum of medical students and facilitate BBN skills acquisition.

Trial registration

ClinicalTrials.gov (NCT05037318), September 8, 2021.