bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Medicaid coverage on receipt of tobacco dependence treatment among Medicaid beneficiaries with substance use disorder
Authors: Patel Sadiq Y. , Wayne Geoffrey F. , Progovac Ana M. , Flores Michael , Moyer Margo , Mullin Brian , Levy Douglas , Saloner Brendan , Cook Benjamin Lê
Published: May 2022

Objective

Individuals with substance use disorder (SUD) smoke cigarettes at a rate that is more than double the rate of the general population. Tobacco dependence treatment (TDT) is effective at reducing smoking, yet it is unclear whether expanding insurance coverage of these services increases TDT use among Medicaid beneficiaries with SUD.

Data Source

2009–2013 Medicaid data in all 50 states and Washington DC.

Study Design

We conducted a retrospective analysis of the 2009–2013 de‐identified Medicaid Analytic Extract (MAX) claims for a 100% national sample of fee‐for‐service (FFS) Medicaid adult beneficiaries. Using a difference‐in‐difference‐in‐differences analysis, we assessed the association of full TDT coverage on TDT medication use and tobacco cessation counseling services between beneficiaries with and without SUD. We adjusted for age, sex, race/ethnicity, diagnosis of co‐occurring chronic illness, state tobacco taxes, and state and year fixed effects.

Data Collection/Extraction Methods

We excluded patients not continuously enrolled in Medicaid for 12 months during the calendar year, adults aged 65 and older (given their dual enrollment in Medicaid and Medicare), minors aged 12–17, and pregnant women (for whom different TDT coverage policies apply).

Principal Findings

We separately modeled the association between full coverage of (1) counseling, (2) over‐the‐counter nicotine replacement therapy, and (3) prescription cessation medications on TDT medication treatment and counseling services. We found that each coverage led to increases in any TDT medication treatment and counseling services for beneficiaries with SUD. The effects of each coverage on medication treatment were greater for beneficiaries with SUD compared to beneficiaries without SUD (ranging from 4.9 to 6.1 percentage point difference).

Conclusion

Coverage of tobacco cessation counseling, over‐the‐counter nicotine replacement therapy, and prescription cessation medications holds promise for reducing the wide disparities in rates of smoking between those with and without SUD.
Impact of time interval between neoadjuvant chemoradiotherapy and surgery on oncological outcomes of locally advanced rectal cancer
Authors: Cheung Irene Hing‐fong , Lo Michelle Hau‐ching , Poon Michael Chi‐ming
Published: May 2022

Background

The optimal interval between completion of neoadjuvant chemoradiotherapy and surgery in rectal adenocarcinoma was controversial.

Aim

To study the impact of standard versus extended time interval for surgery after neoadjuvant chemoradiotherapy in relation to the surgical outcomes in locally advanced rectal cancer.

Method

Retrospective review on consecutive patients with rectal adenocarcinoma completed long course neoadjuvant chemoradiation and surgery in New Territories West cluster, Hong Kong. Patients were divided into three groups according to time interval before surgery: group A (<12 weeks), group B (13–15 weeks) and group C (>15 weeks). Primary outcome was overall recurrence, including local and distant recurrence. Secondary outcomes included surgical morbidities, complete pathological responses and 5‐year survival.

Results

A total of 107 patients were recruited between January 2010 and December 2014. The waiting period had no impact on medical and surgical complications, pathological complete response (pCR), and downstaging effect. Intensive care unit (ICU) admission, and permanent stoma rate were significantly increased with waiting period more than 15 weeks. The 2‐year and 5‐year overall recurrence rate, 5‐year disease‐free and overall survival were similar among the three groups. Time interval of surgery more than 15 weeks had six times higher risk of 5‐year overall recurrence in multivariable logistic regression analysis.

Conclusion

Interval of surgery more than 12 weeks after completion of long course neoadjuvant chemoradiotherapy did not improve oncological outcomes.
Role of radiomics in predicting immunotherapy response
Authors: Kothari Gargi
Published: May 2022

Immunotherapies have revolutionised cancer management. Despite their success, durable responses are limited to a subset of patients. Prediction of immunotherapy response in patients has proven to be difficult due to a lack of robust biomarkers. Routinely collected imaging may offer an additional information source to personalise patient treatment, with advantages over tissue‐based biomarkers. Quantitative image analysis or radiomics, which involves the high‐throughput extraction of imaging features, has the potential to non‐invasively predict cancer histology, outcomes and prognosis. This review evaluates the value of radiomics in patients undergoing immunotherapy, with a summary provided of the performance of radiomics models in predicting immunotherapy response and toxicity, as well as immune correlates. Much of the literature focussed on clinical endpoints and correlates to tissue biomarkers, particularly in lung cancer, while few studies investigated association with immune‐related adverse events. Strengths of the studies included more frequent use of clinical trial datasets, homogenous patient cohorts and high‐quality diagnostic scans. Limitations of the studies include heterogeneity in study methodology, lack of well‐defined homogenous imaging datasets, limited open publishing of imaging datasets, coding and parameters used for radiomics signature development and limited use of external validation datasets. Future research should address the above limitations, as well as further explore the relationship between radiomics and immune‐related adverse effects and less well‐studied biological correlates such tumour mutational burden, and incorporate known clinical prognostic scores into radiomics models.
Comparison of recurrence risk between patients with clinically node‐positive and ‐negative stage I non‐small cell lung cancer following surgery: A propensity score matching analysis
Authors: Huang Kuo‐Yang , Chen Hung‐Jen , Lin Ching‐Hsiung , Wang Bing‐Yen , Cheng Ching‐Yuan , Lin Sheng‐Hao
Published: May 2022

Background

Identifying patients with stage I non‐small cell lung cancer (NSCLC) at increased risk of tumor recurrence following surgery remains a major challenge. The current study aimed to compare disease‐free survival (DFS) rates after surgery between patients with clinically node‐positive (cN+) and ‐negative (cN0) stage I NSCLC.

Methods

Patients with pathological stage I resected NSCLC were identified from the lung cancer database of Changhua Christian Hospital in Taiwan. Patients with clinical N status 1 or 2 and pathological N status 0 were identified as the cN+/pN0 cohort, whereas others were identified as the cN0/pN0 cohort. Propensity score matching (PSM) was used to balance the baseline characteristics between both cohorts. Kaplan–Meier method and Cox proportional hazards model were used to evaluate DFS.

Results

From January 2010 to July 2019, 754 eligible patients were enrolled into the study, among whom 41 (5.4%) were cN+/pN0. The median follow‐up time was 43.4 months. Before PSM, the 5‐year DFS rate was 79.0% and 90.3% in cN+/pN0 and cN0/pN0 cohorts (log‐rank test,p = 0.009), respectively. After a 1:4 PSM, multivariate analysis showed that the cN+/pN0 cohort still had a poorer DFS compared to the cN0/pN0 cohort in (hazard ratio, 3.17;p = 0.040).

Conclusion

Among patients with stage I resected NSCLC, cN+ patients had a worse DFS compared to cN0 patients. Surgeons should therefore consider more aggressive adjuvant therapy or frequent follow‐up in patients with surgically resected stage I NSCLC with cN+ status.
The use of melatonin in Danish intensive care departments—A nationwide observational study
Authors: Sørensen Kasper Mørk , Olesen Charlotte , Meyhoff Christian Sylvest , Andersen Lars Peter Kloster
Published: May 2022

Background

Melatonin is widely employed as a hypnotic in various patient groups. In intensive care patients, melatonin seems to be increasingly used due to potential clinical effects and a favourable safety profile.

Objectives

We aimed to investigate the extend of usage and clinical practice of melatonin therapy in intensive care departments in Denmark.

Design

Data from regional hospital pharmacies and the Danish Intensive Care Database were used to estimate defined daily dose and defined daily dose per 1000 ICU admission days. Also, related expenses in the period 2015–2019. Finally, a questionnaire describing the clinical practice of melatonin therapy was provided to all Danish intensive care departments.

Principal Observations

The usage of melatonin in intensive care departments in Denmark increased from 21,300 DDD (200.0 DDD per 1000 ICU admission days) in 2015 to 52,170 DDD (560.7 DDD per 1000 ICU admission days) in 2019. A total of 32 ICU departments participated in the study (97% of all Danish ICU departments). All included ICU departments employed melatonin as a hypnotic. Nineteen percent of included departments administered melatonin to all admitted patients, whereas 25% of departments rarely administered melatonin. Magistral melatonin 3‐mg tablets was the most employed drug dose/formulation. Increased doses of melatonin were administered in selected patients. Melatonin was considered safe by prescribing clinicians.

Conclusions

Melatonin is widely and increasingly used in Danish intensive care departments. The more than doubled usage of melatonin in the study period advocates for further studies employing validated outcomes of sleep and other patient‐relevant outcomes.

Editorial Comment

This study documents that melatonin is frequently used as a hypnotic in Danish intensive care units during recent years despite a shortage of reliable evidence to support a recommendation to treat with melatonin in this context. These results support a need for conducting clinical trials to determine whether or not there is a beneficial effect of melatonin treatment in critically ill patients.
Non‐enzymatic function of WRN RECQL helicase regulates removal of topoisomerase‐I‐DNA covalent complexes and triggers NF‐κB signaling in cancer
Authors: Gupta Pooja , Majumdar Ananda Guha , Patro Birija Sankar
Published: May 2022

Mutation in Werner (WRN) RECQL helicase is associated with premature aging syndrome (Werner syndrome, WS) and predisposition to multiple cancers. In patients with solid cancers, deficiency of the WRN RECQL helicase is paradoxically associated with enhanced overall survival in response to treatment with TOP1 inhibitors, which stabilize pathological TOP1‐DNA‐covalent‐complexes (TOP1cc) on the genome. However, the underlying mechanism of WRN in development of chemoresistance to TOP1 inhibitors is not yet explored. Our whole‐genome transcriptomic analysis for ~25,000 genes showed robust activation of NF‐κB‐dependent prosurvival genes in response to TOP1cc. CRISPR‐Cas9 knockout, shRNA silencing, and under‐expression of WRN confer high‐sensitivity of multiple cancers to TOP1 inhibitor. We demonstrated that WRN orchestrates TOP1cc repair through proteasome‐dependent and proteasome‐independent process, unleashing robust ssDNA generation. This in turn ensues signal transduction for CHK1 mediated NF‐κB‐activation through IκBα‐degradation and nuclear localization of p65 protein. Intriguingly, our site‐directed mutagenesis and rescue experiments revealed that neither RECQL‐helicase nor DNA‐exonuclease enzyme activity of WRN (WRNE84A, WRNK577M, and WRNE84A‐K577M) were required for TOP1cc removal, ssDNA generation and signaling for NF‐κB activation. In correlation with patient data and above results, the TOP1 inhibitor‐based targeted therapy showed that WRN‐deficient melanoma tumors were highly sensitive to TOP1 inhibition in preclinical in vivo mouse model. Collectively, our findings identify hitherto unknown non‐enzymatic role of WRN RECQL helicase in pathological mechanisms underlying TOP1cc processing and subsequent NF‐κB‐activation, offering a potential targeted therapy for WRN‐deficient cancer patients.
Expression profiles of circular RNA in human placental villus and decidua and prediction of drugs for recurrent spontaneous abortion
Authors: Liu Junwei , Gu Yan , Zhu Weiqiang , Zhang Zhaofeng , Xin Yawei , Shen Yupei , He Lin , Du Jing
Published: May 2022

Problem

We aimed to evaluate potential biomarkers and candidate drugs for recurrent spontaneous abortion (RSA) and explore functional circular RNA pathways involved in regulating RSA.

Method of study

Expression profiles of placental villus and decidua samples derived from females with RSA and those with healthy pregnancies who underwent induced abortion were analyzed using high‐throughput RNA whole transcriptome sequencing. Abnormally expressed circular RNAs in a larger cohort of samples were validated using real‐time quantitative polymerase chain reaction. Drug discovery and molecular docking were performed using online databases and the Autodock tool, respectively.

Results

In total, 2103 and 2160 circular RNAs were detected in three pairs of villi and three pairs of decidual tissues, respectively. A total of 22 circular RNAs, 58 miRNAs, and 393 mRNAs with significantly different expression patterns were identified. Five circular RNAs were verified, and the expression of hsa_circ_0088485 was significantly upregulated in the RSA group (P = .041) with a high area under the curve value (.727), sensitivity (76.5%), and specificity (64.7%). GO and KEGG enrichment analyses indicated that differentially expressed genes were associated with angiogenesis and cell adhesion. Drug discovery and molecular docking were analyzed based on 93 differentially expressed mRNAs of the ceRNA network. A total of 36 chemicals were identified as putative bioactive molecules for RSA, and one representative chemical was identified for docking with six proteins.

Conclusions

These findings provide novel insights into the mechanism of regulation of RSA by circular RNA and its clinical diagnosis and treatment.
Reduction in preterm birth rates during and after the COVID‐19 lockdown in Queensland Australia
Authors: Jasper Brittany , Stillerova Tereza , Anstey Christopher , Weaver Edward
Published: May 2022

Background

Preventative strategies for preterm birth are lacking. Recent evidence proposed COVID‐19 lockdowns may have contributed to changes in preterm birth.

Aims

To determine the prevalence of preterm birth and birth outcomes during and after the COVID‐19 lockdown at the Sunshine Coast University Hospital and the overall state of Queensland, Australia.

Methods

Retrospective cohort analysis of all births in Queensland including the Sunshine Coast University Hospital, during two epochs, April 1–May 31, 2020 (lockdown) and June 1–July 31, 2020 (post‐lockdown), compared to antecedent calendar‐matched periods in 2018–2019. Prevalence of preterm birth, stillbirth, and late terminations were examined.

Results

There were 64 989 births in Queensland from April to July 2018–2020. At the Sunshine Coast University Hospital, there was a significantly higher chance of birth at term during both lockdown (odds ratio (OR) 1.81, 95% CI 1.17, 2.79; P = 0.007) and post‐lockdown (OR 2.01, 95% CI 1.27, 3.18; P = 0.003). At the same centre, prevalence of preterm birth was 5.5% (30/547) during lockdown, compared to 9.1% (100/1095) in previous years, a 40.0% relative reduction (P = 0.016). At this centre during lockdown, emergency caesareans concurrently decreased (P < 0.01) and instrumental vaginal births increased (P < 0.01). In Queensland overall, there was a nonsignificant decrease in the prevalence of preterm birth during lockdown.

Conclusions

There is a link between lockdown and a reduction in the prevalence of preterm birth on the Sunshine Coast. The cause is speculative at present, although increased influenza vaccination rates, decreased transmission of infections, and improved air quality may have been favourable in reducing preterm birth. Further research is needed to determine a causal link.
Birth outcomes by type of attendance at antenatal education: An observational study
Authors: Shand Antonia W. , Lewis‐Jones Bronwyn , Nielsen Timothy , Svensson Jane , Lainchbury Anne , Henry Amanda , Nassar Natasha
Published: May 2022

Background

Antenatal education aims to prepare expectant parents for pregnancy, birth, and parenthood. Studies have reported antenatal education teaching breathing and relaxation methods for pain relief, termed psychoprophylaxis, is associated with reduction in caesarean section rates compared with general birth and parenting classes. Given the rising rates of caesarean section, we aimed to determine whether there was a difference in mode of birth in women based on the type of antenatal education attended.

Materials and methods

A cross‐sectional antenatal survey of nulliparous women ≥28 weeks gestation with a singleton pregnancy was conducted in two maternity hospitals in Sydney, Australia in 2018. Women were asked what type of antenatal education they attended and sent a follow‐up survey post‐birth. Hospital birth data were also obtained. Education was classified into four groups: psychoprophylaxis, birth and parenting, other, or none.

Results

Five hundred and five women with birth data were included. A higher proportion of women who attended psychoprophylaxis education had a vaginal birth (instrumental/spontaneous) (79%) compared with women who attended birth and parenting, other or no education (69%, 67%, 60%, respectively P = 0.045). After adjusting for maternal characteristics, birth and hospital factors, the association was attenuated (odds ratio 2.03; 95% CI 0.93–4.43).

Conclusions

Women who attended psychoprophylaxis couple‐based education had a trend toward higher rates of vaginal birth. Randomised trials comparing different types of antenatal education are required to determine whether psychoprophylaxis education can reduce caesarean section rates and improve other birth outcomes.
Long‐Term Effects of Vietnam War: Agent Orange and the Health of Vietnamese People After 30 Years
Authors: Yamashita Nobuaki , Trinh Trong‐Anh
Published: May 2022

This article examines the long‐term health effects of Agent Orange, a military herbicide containing the hazardous chemical compound dioxin that was widely disseminated in South Vietnam during the Vietnam War (1959–1975). Based on data from US military archives on the herbicide operations, we estimate the prevalence of disabilities among Vietnamese people using the 2009 Population Census. The results demonstrate that the legacy of Agent Orange continues, with ongoing adverse (although small) effects on health even more than 30 years since the end of the war. Critically, the health burden of severe mobility disability has been mostly borne by ethnic minority women in the affected areas.
Successful laparoscopy‐assisted en bloc resection of bulky omental malignant lymphoma involving the ascending colon and multiple lymph node metastases: Report of a technically demanding case in a pediatric patient
Authors: Murakami Masakazu , Muto Mitsuru , Nakagawa Shunsuke , Kedoin Chihiro , Matsui Mayu , Sugita Koshiro , Yano Keisuke , Onishi Shun , Harumatsu Toshio , Yamada Koji , Yamada Waka , Matsukubo Makoto , Kawano Takafumi , Kodama Yuichi , Nishikawa Takuro , Kaji Tatsuru , Okamoto Yasuhiro , Ieiri Satoshi
Published: May 2022

We herein report a 13‐year‐old boy with a chief complaint of abdominal pain and a palpable mass. Contrast‐enhanced computed tomography (CT) scan showed an abdominal bulky tumor involving the ascending colon causing severe stenosis, with multiple abdominal lymph node metastases detected by positron emission tomography (PET)‐CT. Laparoscopic radical resection with right hemicolectomy and lymph node dissection was planned. The bulky tumor was dissected from the retroperitoneum and resected en bloc with the right‐side colon and omentum. The preoperatively detected metastatic lymph nodes were resected along with the tumor. A 6‐cm longitudinal umbilical incision was made, and the huge tumor was removed, with functional end‐to‐end anastomosis performed for intestinal reconstruction. The pathological diagnosis was Burkitt‐like lymphoma with 11q aberration. The postoperative course was uneventful. Laparoscopy‐assisted extirpation is feasible for pediatric solid tumors involving other organs, but indications and procedures should be carefully determined based on preoperative imaging, intraoperative findings and surgeon's skills.
A cross‐sectional survey of risk factors for the presence of Coxiella burnetii in Australian commercial dairy goat farms
Authors: Hou KW , Wiethoelter AK , Stevenson MA , Soares Magalhaes RJ , Lignereux L , Caraguel C , Stenos J , Vincent G , Aleri JW , Firestone SM
Published: May 2022

The largest Australian farm‐based outbreak of Q fever originated from a dairy goat herd. We surveyed commercial dairy goat farms across Australia by testing bulk tank milk (BTM) samples using a commercial indirect enzyme‐linked immunosorbent assay and two quantitative polymerase chain reactions (PCRs). Of the 66 commercial dairy goat herds on record, managers from 61 herds were contacted and 49 provided BTM samples. Five of the surveyed herds were positive on at least one of the diagnostic tests, thus herd‐level apparent prevalence was 10% (95% confidence interval [CI] 4 to 22). True prevalence was estimated to be 3% (95% credible interval: 0 to 18). Herd managers completed a questionnaire on herd management, biosecurity and hygiene practices and risk factors were investigated using multivariable logistic regression. Herds with >900 milking does (the upper quartile) were more likely to be Coxiella burnetii positive (odds ratio = 6.75; 95% CI 1.65 to 27.7) compared with farms with ≤900 milking does. The odds of BTM positivity increased by a factor of 2.53 (95% CI 1.51 to 4.22) for each order of magnitude increase in the number of goats per acre. C. burnetii was not detected in samples from the majority of the Australian dairy goat herds suggesting there is an opportunity to protect the industry and contain this disease with strengthened biosecurity practices. Intensification appeared associated with an increased risk of positivity. Further investigation is required to discriminate the practices associated with an increased risk of introduction to disease‐free herds, from practices associated with maintenance of C. burnetii infection in infected dairy goat herds.
Multiple ovulation and embryo transfer in sheep: Effects of embryo developmental stage and quality on viability in vivo under farm conditions
Authors: King CAF , Osborn D , Grupen CG
Published: May 2022

Multiple ovulation and embryo transfer (MOET) technologies are integral to genetic improvement programs in the sheep industries. Despite the protocols being well established, previous findings regarding the effects of embryo properties on MOET success remain contradictory. The objective of this study was to determine the effects of embryo developmental stage and quality on embryo viability following transfer to recipient ewes. Data including details of 377 embryos collected from 45 Merino donor ewes were obtained from MOET trials conducted on three separate farms on day 6 after laparoscopic artificial insemination (AI). A total of 270 embryos were classified as being of transferrable grade (grade 1: n = 233; grade 2: n = 37). One or two transferrable grade embryos were transferred to each of 256 synchronised recipient ewes and pregnancy diagnosis was performed on day 36 after embryo transfer. Embryos at the hatched blastocyst stage tended to have greater viability in vivo compared to embryos at the late morula stage (59.0 ± 10.6% vs. 36.2 ± 9.7%; P = 0.083). The viability of grade 1 embryos was greater than that of grade 2 embryos (53.6 ± 7.8% vs. 35.9 ± 10.2%; P < 0.05). The results suggest that the success of the MOET trials was influenced by the transfer of embryos at the late morula stage, almost half of which were classified as grade 2 embryos. These findings highlight the importance of following strict embryo quality grading criteria to inform the most economical management of recipient ewes and maximize pregnancy outcomes.
Integrated review of the knowledge, attitudes, and practices of maternity health care professionals concerning umbilical cord clamping
Authors: Peberdy Lisa , Young Jeanine , Massey Debbie , Kearney Lauren
Published: May 2022

Background

Umbilical cord clamp timing has implications for newborn health, which include increased iron stores up to 6 months of age. National and International cord clamping guidelines differ as do health professionals' practices. The rationale for differences in cord clamping practice is unclear.

Aims and objective

Studies on the knowledge, attitudes, and practices of maternity health care professionals about cord clamp timing were synthesized. Similarities and differences between professional groups and understanding of the optimal timing of cord clamp timing for term newborns were compared.

Methods

An integrative review was undertaken. PubMed, Scopus, MIDIRS, CINAHL, and Google Scholar were searched. Publication date limits were set between January 2007 and December 2020. Quality appraisal was undertaken using the Critical Appraisal Skills Program (CASP) tools.

Results

Eighteen studies met inclusion criteria, as they included primary research studies that investigated maternity health care professionals' knowledge, attitudes, and practices about umbilical cord clamping, and were written in English. Four main subject areas were identified: a) knowledge of optimal cord clamp timing; b) attitudes and perceptions of early vs deferred cord clamping; c) cord clamping practice; and d) rationale for cord clamping practice.

Conclusions

Different attitudes and practices were identified between midwifery and medical professionals in relation to cord clamp timing together with health professional knowledge and practice gaps pertaining to optimal cord clamp timing. Contemporary evidence should inform guidelines for clinical practice and be embedded into maternity health professional curricula and professional development programs.
Links between shared and unique perspectives of parental psychological control and adolescent emotional problems: A dyadic daily diary study
Authors: Xu Jingyi , Zheng Yao
Published: May 2022

Using month‐long daily diary data collected between 2019 and 2020 among 99 dyads of Canadian parents (58.6% White, Mage = 43.5, 69.7% female) and adolescents (51.5% White, Mage = 14.6, 53.5% female) from middle to high socioeconomic status families, this study investigated parents' and adolescents' daily shared and unique perceptions of parental psychological control and adolescent emotional problems at within‐ and between‐family level, and examined their cross‐day associations. Multilevel multi‐trait multi‐method confirmatory factor analysis revealed both convergence and divergence across parent–adolescent perceptions at the within level, but no convergence at the between level. Dynamic structural equation modeling revealed cross‐day associations across different perspectives of parenting and adolescent behaviors. Findings contribute novel knowledge to understanding parent–child daily interactions with a multi‐informant approach.
Breast satisfaction in adult women with Turner syndrome—An international survey employing the BREAST‐Q questionnaire
Authors: Idkowiak Jan , Smyth Arlene , Mundy Lily , Wanaguru Amy , Gleeson Helena , Högler Wolfgang
Published: May 2022

Objective

Turner syndrome (TS) is associated with short stature, delayed puberty, primary ovarian insufficiency, and other features. Most girls with TS require oestrogen replacement for pubertal induction. There is paucity of data in adult TS on pubertal outcomes, including breast satisfaction. Here, we assess breast satisfaction in TS with the BREAST‐Q questionnaire, a well‐validated patient‐related outcome measure (PROM).

Design

International survey distributed online through TS support groups.

Patients

Adult women aged 18–45 years with TS (self‐reported).

Measurements

The questionnaire contained demographics, health history and the four domains of the BREAST‐Q. BREAST‐Q scores were matched on a one‐to‐one basis for age, body mass index (BMI) and educational background to a normative data set derived from the ‘Army of Women’, an online community of healthy volunteers.

Results

Of 97 total responses, 74 could be matched to the control cohort. Median age was 32 years (18–45 years) and 97% were White Caucasian. Median age at menarche was 15.5 years (12–34 years), 86% had received pubertal induction therapy as teenagers. We found significantly lower BREAST‐Q scores in TS in the domains ‘Satisfaction with Breast’ (p = .021), ‘Psychosocial Wellbeing’ (p < .0001) and ‘Sexual Wellbeing’ (p < .0001). TS who had received oestrogen replacement therapy reported lower scores compared to TS who had not received oestrogen therapy (p < .0001). Lower BMI and previous growth hormone therapy were associated with lower breast satisfaction.

Conclusions

TS women who received oestrogen replacement for pubertal induction self‐report lower breast satisfaction scores and late menarche, suggesting that type, mode of delivery, dose and timing of hormone supplements merit prospective study.
Dermatoscopically narrowed surgical margins for head and neck basal cell carcinoma: A retrospective case‐control study
Authors: Herzum Astrid , Burlando Martina , Tavilla Pietro Paolo , Micalizzi Claudia , Molle Mattia Fabio , Cozzani Emanuele , Parodi Aurora
Published: May 2022

Background

Basal cell carcinoma (BCC) can cause extensive tissue damage if untreated. Complete surgical excision is the treatment of choice, but especially in the head‐and neck area, defining both radical and healthy skin sparing surgical margins is complex.

Materials and methods

Excised, small (≤ 1 cm), BCCs of the head and neck were retrospectively analyzed, comparing histological properness of surgical margins after clinical‐dermatoscopical preoperative evaluation (cases), vs. clinical evaluation only (controls) and recurrences.

Results

Of 281 BCCs: 6 % (8/139) of cases and 8 % (12/142) of controls had unproper deep margins; 4 % (5/139) of cases, 20 % (29/142) of controls had unproper lateral margins (P < 0.001). Surgical 3 mm lateral margins were unproper in 0 % (15/66) of cases, 15 % (10/66) of controls (P > 0.005); surgical 1–2 mm lateral margins were unproper in 7 % (5/73) of cases, 25 % (19/76) of controls (P < 0.01). Of cases excised at 3 mm, 1–2 mm, and controls, 1.5 %, 0 %, and 7.7 % recurred, respectively.

Conclusions

BCC excision at 3 mm may be appropriate in the head and neck for small, dermatoscopically well‐defined and non‐aggressive BCCs, attaining surgical cure rates of 100 % and 1.5 % recurrences. Excision at 1–2 mm should be reserved only for BCCs in very difficult‐to‐treat areas, as the surgical cure rate was only 93 %.
Inducible and tissue‐specific cell labeling in Cre‐ERT2 transgenic Xenopus lines
Authors: Lin Tzi‐Yang , Taniguchi‐Sugiura Yuka , Murawala Prayag , Hermann Sarah , Tanaka Elly M.
Published: May 2022

Investigating cell lineage requires genetic tools that label cells in a temporal and tissue‐specific manner. The bacteriophage‐derived Cre‐ERT2/loxP system has been developed as a genetic tool for lineage tracing in many organisms. We recently reported a stable transgenic Xenopus line with a Cre‐ERT2/loxP system driven by the mouse Prrx1 (mPrrx1) enhancer to trace limb fibroblasts during the regeneration process (Prrx1:CreER line). Here we describe the detailed technological development and characterization of such line. Transgenic lines carrying a CAG promoter‐driven Cre‐ERT2/loxP system showed conditional labeling of muscle, epidermal, and interstitial cells in both the tadpole tail and the froglet leg upon 4‐hydroxytamoxifen (4OHT) treatment. We further improved the labeling efficiency in the Prrx1:CreER lines from 12.0% to 32.9% using the optimized 4OHT treatment regime. Careful histological examination showed that Prrx1:CreER lines also sparsely labeled cells in the brain, spinal cord, head dermis, and fibroblasts in the tail. This work provides the first demonstration of conditional, tissue‐specific cell labeling with the Cre‐ERT2/loxP system in stable transgenic Xenopus lines.
Early intervention for very young children with or at high likelihood for autism spectrum disorder: An overview of reviews
Authors: Franz Lauren , Goodwin Cara D. , Rieder Amber , Matheis Maya , Damiano Diane L.
Published: May 2022

Aim

To identify which interventions are supported by evidence and the quality of that evidence in very young children with or at high likelihood for autism spectrum disorder (ASD) to improve child outcomes.

Method

We conducted an overview of reviews to synthesize early intervention literature for very young children with or at high likelihood for ASD. Cochrane guidance on how to perform overviews of reviews was followed. Comprehensive searches of databases were conducted for systematic reviews and meta‐analyses between January 2009 and December 2020. Review data were extracted and summarized and methodological quality was assessed. Primary randomized controlled trial evidence was summarized and risk of bias assessed. This overview of reviews was not registered.

Results

From 762 records, 78 full texts were reviewed and seven systematic reviews and meta‐analyses with 63 unique studies were identified. Several interventional approaches (naturalistic developmental behavioral intervention, and developmental and behavioral interventions) improved child developmental outcomes. Heterogeneity in design, intervention and control group, dose, delivery agent, and measurement approach was noted. Inconsistent methodological quality and potential biases were identified.

Interpretation

While many early interventional approaches have an impact on child outcomes, study heterogeneity and quality had an impact on our ability to draw firm conclusions regarding which treatments are most effective. Advances in trial methodology and design, and increasing attention to mitigating measurement bias, will advance the quality of the ASD early intervention evidence base.

What this paper adds

Naturalistic developmental behavioral interventions, as well as developmental and behavioral interventions, improve child outcomes in autism spectrum disorder (ASD).

If only randomized controlled trials are considered, guidelines for early intensive behavioral intervention in younger children should be revisited.

The greatest intervention impacts were on proximal, intervention‐specific outcomes.

Inadequacies in the quality of the early ASD intervention evidence base were observed.
A double‐blind, Randomized controlled trial on glucose‐lowering EFfects and safety of adding 0.25 or 0.5 mg lobeglitazone in type 2 diabetes patients with INadequate control on metformin and dipeptidyl peptidase‐4 inhibitor therapy: REFIND study
Authors: Ryang Soree , Kim Sang Soo , Bae Ji Cheol , Han Ji Min , Kwon Su Kyoung , Kim Young Il , Nam‐Goong Il Seong , Kim Eun Sook , Kim Mi‐kyung , Lee Chang Won , Yoo Soyeon , Koh Gwanpyo , Kwon Min Jeong , Park Jeong Hyun , Kim In Joo
Published: May 2022

Aims

To compare the efficacy and safety of adding low‐dose lobeglitazone (0.25 mg/day) or standard‐dose lobeglitazone (0.5 mg/day) to patients with type 2 diabetes mellitus (T2DM) with inadequate glucose control on metformin and dipeptidyl peptidase (DPP4) inhibitor therapy.

Materials and Methods

In this phase 4, multicentre, double‐blind, randomized controlled, non‐inferiority trial, patients with T2DM insufficiently controlled by metformin and DPP4 inhibitor combination therapy were randomized to receive either low‐dose or standard‐dose lobeglitazone. The primary endpoint was non‐inferiority of low‐dose lobeglitazone in terms of glycaemic control, expressed as the difference in mean glycated haemoglobin levels at week 24 relative to baseline values and compared with standard‐dose lobeglitazone, using 0.5% non‐inferiority margin.

Results

At week 24, the mean glycated haemoglobin levels were 6.87 ± 0.54% and 6.68 ± 0.46% in low‐dose and standard‐dose lobeglitazone groups, respectively (p = .031). The between‐group difference was 0.18% (95% confidence interval 0.017‐0.345), showing non‐inferiority of the low‐dose lobeglitazone. Mean body weight changes were significantly greater in the standard‐dose group (1.36 ± 2.23 kg) than in the low‐dose group (0.50 ± 1.85 kg) at week 24. The changes in HOMA‐IR, lipid profile and liver enzyme levels showed no significant difference between the groups. Overall treatment‐emergent adverse events (including weight gain, oedema and hypoglycaemia) occurred more frequently in the standard‐dose group.

Conclusions

Adding low‐dose lobeglitazone to metformin and DPP4 inhibitor combination resulted in a non‐inferior glucose‐lowering outcome and fewer adverse events compared with standard‐dose lobeglitazone. Therefore, low‐dose lobeglitazone might be one option for individualized strategy in patients with T2DM.
Type 2 diabetes subgroups and response to glucose‐lowering therapy: Results from the EDICT and Qatar studies
Authors: Abdul‐Ghani Tamam , Puckett Curtiss , Migahid Osama , Abdelgani Siham , Migahed Ayman , Adams John , Triplitt Curtis , DeFronzo Ralph , Jayyousi Amin , Abdul‐Ghani Muhammad
Published: May 2022

Aim

To examine the efficacy of glucose‐lowering medications in subgroups of patients with type 2 diabetes mellitus (T2DM).

Research design and methods

Cluster analysis was performed in participants in the Efficacy and Durability of Initial Combination Therapy for Type 2 Diabetes (EDICT) study and the Qatar study using age, body mass index (BMI), glycated haemoglobin (HbA1c), and homeostatic model assessment of insulin resistance (HOMA‐IR) and beta‐cell function (HOMA‐β). Participants also underwent an oral glucose tolerance test with measurement of plasma glucose, insulin and C‐peptide concentrations to derive independent measures of insulin secretion and insulin sensitivity. The response to glucose‐lowering therapies (change in HbA1c) was measured in each participant cluster for 3 years.

Results

Three distinct and comparable clusters/groups of T2DM patients were identified in both the EDICT and Qatar studies. Participants in Group 1 had the highest HbA1c and manifested severe insulin deficiency. Participants in Group 3 had comparable insulin sensitivity to those in Group 1 but better beta‐cell function and better glucose control. Participants in Group 2 had the highest BMI with severe insulin resistance accompanied by marked hyperinsulinaemia, which was primarily attributable to decreased insulin clearance. Unexpectedly, participants in Group 1 had better response to combination therapy with pioglitazone plus exenatide than with insulin therapy or metformin sequentially followed by glipizide and basal insulin, while participants in Group 2 responded equally well to both therapies despite very severe insulin resistance.

Conclusion

Distinct metabolic phenotypes characterize different T2DM clusters and differential responses to glucose‐lowering therapies. Participants with severe insulin deficiency respond better to agents that preserve beta‐cell function, while, surprisingly, patients with severe insulin resistance did not respond favourably to insulin sensitizers.
Severity of deforestation mediates biotic homogenisation in an island archipelago
Authors: Mitchell Simon L. , Edwards David P. , Martin Rob W. , Deere Nicolas J. , Voigt Maria , Kastanya Agustinus , Karja Adi , Akbar Panji Gusti , Jordan Khaleb , Tasirin John , Zakaria Zuliyanto , Martin Tom , Supriatna Jatna , Winarni Nurul , Davies Zoe G. , Struebig Matthew J.
Published: May 2022

Anthropogenic‐driven species extinctions are radically changing the biosphere. Biological communities may become increasingly similar to or dissimilar from one another via the processes of biotic homogenisation or heterogenisation. A key question is how the conversion of native forests to agriculture may influence these processes by driving changes in the occurrence patterns of restricted‐range endemic species versus wide‐ranging generalists. We examined biotic homogenisation and heterogenisation in bird communities on the Southeast Asian islands of Borneo, Sulawesi, Seram, Buru, Talaud and Sangihe. Each island is characterised by high levels of avian endemism and unique spatial configuration of forest conversion to agriculture. Forest conversion to agriculture influenced the patterns of biotic homogenisation on five islands. Bird communities became increasingly dissimilar to forest reference communities relative to localised patterns of deforestation. Turnover led to species with larger global range‐sizes dominating communities at the expense of island endemics and ecological specialists. Within islands, forest conversion did not result in clear changes to β‐diversity, whereas between‐island communities became increasingly similar with greater deforestation, implying that patterns of forest conversion profoundly affect biotic homogenisation. Our findings elucidate how continued conversion of forests is causing the replacement of endemic species by a small cohort of shared ubiquitous species with potentially strong negative consequences for ecosystem functioning and resilience. Halting reorganisation of the biosphere via the loss of range‐restricted species and spread of wide‐ranged generalists will require improved efforts to reduce the impacts of deforestation, particularly in regions with high endemism.
Implementation of a food science and nutrition module in a dental undergraduate curriculum
Authors: Crowe Michael , O'Sullivan Michael , Winning Lewis , Cassetti Oscar , O'Connell Brian , O'Sullivan Aifric , Gibney Eileen , Doyle Suzanne L. , Bennett Annemarie , Moynihan Paula
Published: May 2022

Introduction

To outline the development and implementation of a food science and nutrition module for dental undergraduate students that provides basic knowledge and clinical skills for improving oral health outcomes and understanding their importance for overall health.

Materials and methods

Interdisciplinary discussions with professionals with expertise in food science and nutrition, including dentists, dietitians and nutritionists, were held to agree on core subject areas in line with the evidence base. The module was delivered online to 2nd‐year dental students due to COVID‐19 restrictions. Students completed an online evaluation on completing the module. Final examination consisted of one essay question.

Results

Subject areas and learning outcomes were derived from current and previous approaches to curriculum development. A total of 14 prerecorded lectures, including healthy eating guidelines, dietary assessment, specific oral effects of diet and food constituents were delivered and tutorials provided. The evaluation survey had a 90% (n = 39/43) response rate. A majority indicated that the course was “interesting,” “worth doing” (59%) and “provided a good evidence base to understand nutrition and oral health” (87%). Nearly all students (92%) agreed that the course was “sufficiently structured to allow understanding of the key topics” and that “a good understanding of nutrition is important for a dentist” (95%).

Conclusion

A food science and nutrition module developed by a multidisciplinary team enabled dental students to gain an understanding of the role of diet in oral and overall health. The module facilitated the development of skills that enable students to utilise dietary assessment techniques and promote dietary interventions beneficial to oral health. The approach taken may act as a template for other institutions.
Altered grey matter integrity and network vulnerability relate to epilepsy occurrence in patients with multiple sclerosis
Authors: Ciolac Dumitru , Gonzalez‐Escamilla Gabriel , Winter Yaroslav , Melzer Nico , Luessi Felix , Radetz Angela , Fleischer Vinzenz , Groppa Stanislav A. , Kirsch Michael , Bittner Stefan , Zipp Frauke , Muthuraman Muthuraman , Meuth Sven G. , Grothe Matthias , Groppa Sergiu
Published: May 2022

Background and purpose

The aim of this study was to investigate the relevance of compartmentalized grey matter (GM) pathology and network reorganization in multiple sclerosis (MS) patients with concomitant epilepsy.

Methods

From 3‐T magnetic resonance imaging scans of 30 MS patients with epilepsy (MSE group; age 41 ± 15 years, 21 females, disease duration 8 ± 6 years, median Expanded Disability Status Scale [EDSS] score 3), 60 MS patients without epilepsy (MS group; age 41 ± 12 years, 35 females, disease duration 6 ± 4 years, EDSS score 2), and 60 healthy subjects (HS group; age 40 ± 13 years, 27 females) the regional volumes of GM lesions and of cortical, subcortical and hippocampal structures were quantified. Network topology and vulnerability were modelled within the graph theoretical framework. Receiver‐operating characteristic (ROC) curve analysis was applied to assess the accuracy of GM pathology measures to discriminate between MSE and MS patients.

Results

Higher lesion volumes within the hippocampus, mesiotemporal cortex and amygdala were detected in the MSE compared to the MS group (all p < 0.05). The MSE group had lower cortical volumes mainly in temporal and parietal areas compared to the MS and HS groups (all p < 0.05). Lower hippocampal tail and presubiculum volumes were identified in both the MSE and MS groups compared to the HS group (all p < 0.05). Network topology in the MSE group was characterized by higher transitivity and assortativity, and higher vulnerability compared to the MS and HS groups (all p < 0.05). Hippocampal lesion volume yielded the highest accuracy (area under the ROC curve 0.80 [0.67–0.91]) in discriminating between MSE and MS patients.

Conclusions

High lesion load, altered integrity of mesiotemporal GM structures, and network reorganization are associated with a greater propensity for epilepsy occurrence in people with MS.
Epilepsy Milestones 2.0: An updated framework for assessing epilepsy fellowships and fellows
Authors: Thio Liu Lin , Edgar Laura , Ali Imran , Farooque Pue , Holland Katherine D. , Mizrahi Eli M. , Shahid Asim M. , Shin Hae Won , Yoo Ji Yeoun , Carlson Chad
Published: May 2022

Objective

Accreditation Council for Graduate Medical Education (ACGME)‐accredited epilepsy fellowships, like other ACGME accredited training programs, use Milestones to establish learning objectives and to evaluate how well trainees are achieving these goals. The ACGME began developing the second iteration of the Milestones 6 years ago, and these are now being adapted to all specialties. Here, we describe the process by which Epilepsy Milestones 2.0 were developed and summarize them.

Methods

A work group of nine board‐certified, adult and pediatric epileptologists reviewed Epilepsy Milestones 1.0 and revised them using a modified Delphi approach.

Results

The new Milestones share structural changes with all other specialties, including a clearer stepwise progression in professional development and the harmonized Milestones that address competencies common to all medical fields. Much of the epilepsy‐specific content remains the same, although a major addition is a set of Milestones focused on reading and interpreting electroencephalograms (EEGs), which the old Milestones lacked. Epilepsy Milestones 2.0 includes a Supplemental Guide to help program directors implement the new Milestones. Together, Epilepsy Milestones 2.0 and the Supplemental Guide recognize advances in epilepsy, including stereo‐EEG, neurostimulation, genetics, and safety in epilepsy monitoring units.

Significance

Epilepsy Milestones 2.0 address the shortcomings of the old Milestones and should facilitate the assessment of epilepsy fellowships and fellows by program directors, faculty, and fellows themselves.