bluuebunny/crossref_metadata_2025 huggingface dataset:
Safe femoral condyle range for the reverse Rigidfix femoral fixation device in anterior cruciate ligament reconstruction
Authors: Luo Zhongliu , Hu Yong , Han Qingmin , Gao Zhi , Cheng Songmiao
Published: March 2022

Background

To determine the characteristics of cross-pin protrusion in patients treated with the reverse Rigidfix femoral fixation device for femoral tunnel preparation through the anteromedial portal in Arthroscopic anterior cruciate ligament reconstruction (ACLR), analyse the reasons for this outcome, and identify safety hazards of this surgical technique for improvement.

Methods

A retrospective analysis of patients who underwent ACLR using this technology at our hospital in 2018 was conducted. Patients with and without cross-pin protrusion were included in the protrusion positive and negative groups, respectively. The sex, age and imaging characteristics of the patients with cross-pin protrusion were identified, and the reasons for cross-pin protrusion were analysed.

Results

There were 64 and 212 patients in the protrusion positive and negative groups, respectively. The proportion of cross-pin protrusion cases was 23.19% (64/276). There was a significant difference in the ratio of males to females (P < 0.001, χ2 = 185.184), the mediolateral femoral condyle diameter (protrusion positive group, 70.59 ± 2.51 mm; protrusion negative group, 82.65 ± 4.16 mm; P < 0.001, t = 28.424), and the anteroposterior diameter of the lateral femoral condyle (protrusion positive group, 58.34 ± 2.89 mm; protrusion negative group, 66.38 ± 3.53 mm; P < 0.001, t = 16.615). The cross-pins did not penetrate the lateral femoral condyle cortex in patients with a mediolateral femoral condyle diameter ≥ 76 mm, but the cross-pins definitely penetrated the cortex when the diameter was ≤ 70 mm. The cross-pins did not penetrate when the anteroposterior lateral femoral condyle diameter was ≥ 66 mm, but the cross-pins definitely penetrated it when the diameter was ≤ 59 mm.

Conclusion

The patients with cross-pin protrusion after reverse Rigidfix femoral fixation treatment to prepare the femoral tunnel through the anteromedial portal in ACLR were mainly females with small femoral condyles. For patients with a mediolateral femoral condyle diameter ≥ 76 mm and an anteroposterior lateral femoral condyle diameter ≥ 66 mm, there is no risk of cross-pin protrusion, so this technique can be used with confidence.

Levels of evidence

III.
Breast adenoid cystic carcinoma: a report of seven cases and literature review
Authors: Zhang Meilin , Liu Yanbiao , Yang Hongguang , Jin Feng , Zheng Ang
Published: March 2022

Background

Primary adenoid cystic carcinoma (ACC) of breast is rarely seen clinically. It is a special subtype of triple-negative breast cancer characterized by low expression of Ki-67, low malignant potential, slow progression and favorable prognosis. To date, treatment for this disease is controversial and no consensus is reached. We analyzed clinical manifestations and pathological characteristics of seven primary breast ACC cases and reported in combination with literature review to promote understanding, diagnosis and treatment of this disease.

Case presentation

We collected seven breast ACC cases pathologically diagnosed and treated in Department of breast surgery of the First Affiliated Hospital of China Medical University from January 2015 to December 2018. We organized and summarized the clinical, imaging, pathological and prognostic information and performed statistical analysis. The median age was 60 years (ranging from 54 to 64 years). Tumors of all patients were detected by immunohistochemistry. Molecular types were mostly triple negative (4/7), and Ki-67 expression was low (5/7). Lymph node metastases were absent in all patients received axillary lymph node surgery. Median follow-up time was 39 months (ranging from 25 to 68 months). There was no occurrence of relapse, distant metastasis or death.

Conclusion

Breast ACC is accompanied with favorable diagnosis, which is different from typical triple-negative breast cancer. Accurate diagnosis of ACC is particularly important.
Solo-surgeon pure laparoscopic donor nephrectomy using passive camera holder: IDEAL stage 2a study
Authors: An Dong Hyeon , Han Jae Hyeon , Jang Myoung Jin , Aum Joomin , Kim Yu Seon , Jeong In Gab , Hong Bumsik , You Dalsan
Published: March 2022

Background

Solo-surgery can be defined as a practice of a surgeon operating alone using a camera holder, without other surgical members except for a scrub nurse. This study was designed to evaluate the feasibility and safety of solo-surgeon pure laparoscopic donor nephrectomy.

Methods

The study protocol was approved by the Institutional Review Board of Asan Medical Center, Seoul, Korea. The brief study protocol was registered on the Clinical Research Information Service site of the Korea Centers for Disease Control and Prevention. Candidates fulfilling all inclusion and exclusion criteria were enrolled in the clinical trial and underwent solo-surgeon pure laparoscopic donor nephrectomy. The feasibility was assessed by the proportion of subjects who could undergo solo-surgeon pure laparoscopic donor nephrectomy without difficulty. The perioperative complications were identified to assess the safety of solo-surgeon pure laparoscopic donor nephrectomy.

Results

Of the 47 potential candidates from November 2018 to August 2019, 40 were enrolled in the clinical trial and seven excluded due to declining participation. The feasibility of solo-surgeon pure laparoscopic donor nephrectomy was 100%, without an occasion of any difficulty requiring conversion to the human assisted pure laparoscopic donor nephrectomy. Fourteen intraoperative complications occurred in 10 patients. The most common intraoperative complication was spleen injury. Two of three cases classified as the Satava classification grade II were due to the incomplete stapling of endoscopic stapler. Seventy-eight postoperative complications occurred in 34 patients. The most common postoperative complication was nausea/vomiting and followed by aspartate aminotransferase/alanine aminotransferase elevation. Most postoperative complication was independent of the solo-surgery itself.

Conclusions

Solo-surgeon pure laparoscopic donor nephrectomy using passive camera holder is technically feasible. In terms of safety, it is necessary to adjust the scope of surgery performed alone.

Trial Registration CRIS, KCT0003458. Registered 30/01/2019, Retrospectively registered, https://cris.nih.go.kr/cris/search/detailSearch.do/15868.
Ultrasound grayscale ratio: a reliable parameter for differentiating between papillary thyroid microcarcinoma and micronodular goiter
Authors: Gong Yun , Yao Xiuzhen , Yu Lifang , Wei Peiying , Han Zhijiang , Fang Jianhua , Ao Weiqun , Xu Chenke
Published: March 2022

Background

The present study aimed to quantify and differentiate the echo levels of papillary thyroid microcarcinomas (PTMCs) and micronodular goiters (MNGs) using the ultrasound grayscale ratio (UGSR) and to investigate the repeatability of UGSR.

Methods

The ultrasound (US) data of 241 patients with 265 PTMCs and 141 patients with 168 MNGs confirmed by surgery and pathology were retrospectively analyzed. All patients had received outpatient ultrasonic examination and preoperative ultrasonic positioning. The RADinfo radiograph reading system was used to measure the grayscales of PTMC, MNG, and thyroid tissues at the same gain level, and the UGSR values of the PTMC, MNG, and thyroid tissue were calculated. The patients were divided into outpatient examination, preoperative positioning, and mean value groups, and the receiver operating characteristic (ROC) curves were calculated to obtain the optimal UGSR threshold to distinguish PTMC from MNG. The interclass correlation coefficient (ICC) was used to assess the consistency of UGSR measured in three groups.

Results

The UGSR values of the PTMC and MNG were 0.56 ± 0.14 and 0.80 ± 0.19 (t = 5.84, P < 0.001) in the outpatient examination group, 0.55 ± 0.14 and 0.80 ± 0.19 (t = 18.74, P < 0.001) in the preoperative positioning group, and 0.56 ± 0.12 and 0.80 ± 0.18 (t = 16.49, P < 0.001) in the mean value group. The areas under the ROC curves in the three groups were 0.860, 0.856, and 0.875, respectively. When the UGSR values for the outpatient examination, preoperative positioning, and mean value groups were 0.649, 0.646, and 0.657, respectively, each group obtained its largest Youden index. A reliable UGSR value was obtained between the outpatient examination and preoperative positioning groups (ICC = 0.79, P = 0.68).

Conclusion

UGSR is a simple and repeatable method to distinguish PTMC from MNG, and hence, can be widely applicable.
Breast cancer morbidity and mortality in rural Ethiopia: data from 788 verbal autopsies
Authors: Ayele Wondimu , Führer Amand , Braun Gabriele Anna , Formazin Franziska , Wienke Andreas , Taylor Lesley , Unverzagt Susanne , Addissie Adamu , Kantelhardt Eva J.
Published: March 2022

Introduction

In Ethiopia, breast cancer is the leading cause of cancer among women. Little is known about the duration of disease and symptoms of patients who died from breast cancer in rural Ethiopia. The objective of this study was to assess breast cancer mortality with a particular focus on the self-reported duration of illness including suffering of symptoms, and need for medical care.

Methods

The cause of death was determined among randomly selected Ethiopian women residing in western Ethiopia. A modified standard verbal autopsy (VA) questionnaire was completed by women whose sisters had died. The questionnaires were reviewed by two independent local physicians to assign a cause of death. We analyzed pattern of cause of deaths, duration of suffering, symptoms, and treatment received.

Result

In our study, the age at death was very similar to other population-based data from Ethiopia. We found 32% of 788 deaths were caused by communicable diseases, 12.1% by neoplasms, and 9.4% by pregnancy/maternal mortality. Breast cancer was the second leading neoplasm, responsible for 21 (2.7%) of all deaths (95% CI 1.5–3.7%), and was among the top five causes of non-communicable deaths. The median age of breast cancer death was 37 years, younger than for other causes of death. The median duration of illness with breast cancer was around 1 year. This was substantially more compared to the duration of infectious diseases, but less than the duration of reproductive neoplasms, diabetes, and epilepsy.

Discussion/conclusion

Breast cancer deaths are common causes of death in women of rural Ethiopia. When assessing the total duration of illness according to specific causes of death, breast and other cancers accounted for a large share of the burden. This has practical implications and highlights the need for palliative care for cancer patients. Substantial efforts are necessary to improve early detection and treatment for breast cancer to reduce premature death in women.
The process of learning the autogenic training relaxation technique and its benefits on the wellness of people living with HIV
Authors: Ramirez Garcia Maria Pilar , Leclerc-Loiselle Jérôme , Côté José , Brouillette Marie-Josée , Thomas Réjean
Published: March 2022

Background

Various mind-body practices are used by people living with HIV to promote their general well-being. Among these is autogenic training (AT), a self-guided relaxation technique requiring regular practice for observable benefits. However, little has been written about the process of learning this technique, which is obviously a prerequisite to regular practice. This study therefore aims to describe the process by which people living with HIV learn AT.

Methods

The study is a descriptive qualitative study using semi-structured interviews and a thematic analysis with a mixed approach. Fourteen participants living with HIV completed sessions to learn autogenic training over a period of 3 months.

Results

The process of learning AT was approached through three themes: initiating the learning process, taking ownership of the technique, and observing its benefits on wellness. To initiate learning, participants had to express a need to take action on an aspect of their well-being and their openness to complementary approaches to care. Taking ownership of the technique was facilitated by guidance from the nurse researcher, the participants’ personal adaptations to overcome barriers to their practice, regular practice, and rapid observation of its benefits. Finally, the participants reported the observation of benefits on their wellness, including personal development, mainly in terms of the creative self, the essential self, and the coping self. This perception of the technique’s benefits was part of the learning process, as it contributed both to the participants’ ownership of the technique and to reinforcing their AT practice.

Conclusions

People living with HIV see learning AT as a progressive process, in which wellness is a major outcome and a contributing factor in developing a regular practice.
CRISPR based therapeutics: a new paradigm in cancer precision medicine
Authors: Das Sumit , Bano Shehnaz , Kapse Prachi , Kundu Gopal C.
Published: March 2022

Background

Clustered regularly interspaced short palindromic repeat (CRISPR)-CRISPR-associated protein (Cas) systems are the latest addition to the plethora of gene-editing tools. These systems have been repurposed from their natural counterparts by means of both guide RNA and Cas nuclease engineering. These RNA-guided systems offer greater programmability and multiplexing capacity than previous generation gene editing tools based on zinc finger nucleases and transcription activator like effector nucleases. CRISPR-Cas systems show great promise for individualization of cancer precision medicine.

Main body

The biology of Cas nucleases and dead Cas based systems relevant for in vivo gene therapy applications has been discussed. The CRISPR knockout, CRISPR activation and CRISPR interference based genetic screens which offer opportunity to assess functions of thousands of genes in massively parallel assays have been also highlighted. Single and combinatorial gene knockout screens lead to identification of drug targets and synthetic lethal genetic interactions across different cancer phenotypes. There are different viral and non-viral (nanoformulation based) modalities that can carry CRISPR-Cas components to different target organs in vivo.

Conclusion

The latest developments in the field in terms of optimization of performance of the CRISPR-Cas elements should fuel greater application of the latter in the realm of precision medicine. Lastly, how the already available knowledge can help in furtherance of use of CRISPR based tools in personalized medicine has been discussed.
Liquid biopsy at the frontier of detection, prognosis and progression monitoring in colorectal cancer
Authors: Zhou Hui , Zhu Liyong , Song Jun , Wang Guohui , Li Pengzhou , Li Weizheng , Luo Ping , Sun Xulong , Wu Jin , Liu Yunze , Zhu Shaihong , Zhang Yi
Published: March 2022

Colorectal cancer (CRC) is one of the most common cancers worldwide and a leading cause of carcinogenic death. To date, surgical resection is regarded as the gold standard by the operator for clinical decisions. Because conventional tissue biopsy is invasive and only a small sample can sometimes be obtained, it is unable to represent the heterogeneity of tumor or dynamically monitor tumor progression. Therefore, there is an urgent need to find a new minimally invasive or noninvasive diagnostic strategy to detect CRC at an early stage and monitor CRC recurrence. Over the past years, a new diagnostic concept called “liquid biopsy” has gained much attention. Liquid biopsy is noninvasive, allowing repeated analysis and real-time monitoring of tumor recurrence, metastasis or therapeutic responses. With the advanced development of new molecular techniques in CRC, circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), exosomes, and tumor-educated platelet (TEP) detection have achieved interesting and inspiring results as the most prominent liquid biopsy markers. In this review, we focused on some clinical applications of CTCs, ctDNA, exosomes and TEPs and discuss promising future applications to solve unmet clinical needs in CRC patients.
Targeting the histone H3 lysine 79 methyltransferase DOT1L in MLL-rearranged leukemias
Authors: Yi Yan , Ge Shenglei
Published: March 2022

Disrupting the methylation of telomeric silencing 1-like (DOT1L)-mediated histone H3 lysine 79 has been implicated in MLL fusion-mediated leukemogenesis. Recently, DOT1L has become an attractive therapeutic target for MLL-rearranged leukemias. Rigorous studies have been performed, and much progress has been achieved. Moreover, one DOT1L inhibitor, EPZ-5676, has entered clinical trials, but its clinical activity is modest. Here, we review the recent advances and future trends of various therapeutic strategies against DOT1L for MLL-rearranged leukemias, including DOT1L enzymatic activity inhibitors, DOT1L degraders, protein–protein interaction (PPI) inhibitors, and combinatorial interventions. In addition, the limitations, challenges, and prospects of these therapeutic strategies are discussed. In summary, we present a general overview of DOT1L as a target in MLL-rearranged leukemias to provide valuable guidance for DOT1L-associated drug development in the future. Although a variety of DOT1L enzymatic inhibitors have been identified, most of them require further optimization. Recent advances in the development of small molecule degraders, including heterobifunctional degraders and molecular glues, provide valuable insights and references for DOT1L degraders. However, drug R&D strategies and platforms need to be developed and preclinical experiments need to be performed with the purpose of blocking DOT1L-associated PPIs. DOT1L epigenetic-based combination therapy is worth considering and exploring, but the therapy should be based on a thorough understanding of the regulatory mechanism of DOT1L epigenetic modifications.
Statistical and machine learning methods for spatially resolved transcriptomics data analysis
Authors: Zeng Zexian , Li Yawei , Li Yiming , Luo Yuan
Published: March 2022

The recent advancement in spatial transcriptomics technology has enabled multiplexed profiling of cellular transcriptomes and spatial locations. As the capacity and efficiency of the experimental technologies continue to improve, there is an emerging need for the development of analytical approaches. Furthermore, with the continuous evolution of sequencing protocols, the underlying assumptions of current analytical methods need to be re-evaluated and adjusted to harness the increasing data complexity. To motivate and aid future model development, we herein review the recent development of statistical and machine learning methods in spatial transcriptomics, summarize useful resources, and highlight the challenges and opportunities ahead.
Pan-cancer predictions of transcription factors mediating aberrant DNA methylation
Authors: Detilleux Dylane , Spill Yannick G. , Balaramane Delphine , Weber Michaël , Bardet Anaïs Flore
Published: March 2022

Background

Aberrant DNA methylation is a hallmark of cancer cells. However, the mechanisms underlying changes in DNA methylation remain elusive. Transcription factors initially thought to be repressed from binding by DNA methylation, have recently emerged as being able to shape DNA methylation patterns.

Results

Here, we integrated the massive amount of data available from The Cancer Genome Atlas to predict transcription factors driving aberrant DNA methylation in 13 cancer types. We identified differentially methylated regions between cancer and matching healthy samples, searched for transcription factor motifs enriched in those regions and selected transcription factors with corresponding changes in gene expression. We predict transcription factors known to be involved in cancer as well as novel candidates to drive hypo-methylated regions such as FOXA1 and GATA3 in breast cancer, FOXA1 and TWIST1 in prostate cancer and NFE2L2 in lung cancer. We also predict transcription factors that lead to hyper-methylated regions upon transcription factor loss such as EGR1 in several cancer types. Finally, we validate that FOXA1 and GATA3 mediate hypo-methylated regions in breast cancer cells.

Conclusion

Our work highlights the importance of some transcription factors as upstream regulators shaping DNA methylation patterns in cancer.
Adherence to a guided walking program with amelioration of cognitive functions in subjects with schizophrenia even during COVID-19 pandemic
Authors: Mandini S. , Morelli M. , Belvederi Murri M. , Grassi L. , Masotti S. , Simani L. , Zerbini V. , Raisi A. , Piva T. , Grazzi G. , Mazzoni G.
Published: March 2022

Background

Aim of the study was to enrol a group of individuals with schizophrenia in a long-term moderate-intensity physical activity program and to evaluate its effects on their cognitive functions and cardiovascular risk factors. An additional aim of the study was the comparison of the adherence to the physical activity program before and during the COVID-19 pandemic.

Methods

Forty sedentary patients diagnosed with schizophrenia (mean age 46.4 ± 9.6) followed by the Public Mental Health Department of Ferrara were included in the study. 28 of them followed a 1-year walking program consisting of two guided walking sessions/week, while 12 maintained their sedentary lifestyle and followed the usual Cognitive Rehabilitation program. To the participants following the walking program VO2 peak and walking speed were assessed at baseline and at the end of the program. All participants were evaluated on blood pressure and anthropometric variable. Cognitive functions were assessed with the Screen for Cognitive Impairment in Psychiatry (SCIP) and with the Frontal Assessment Battery (FAB) questionnaires.

Results

The 20 participants completing the walking program displayed significant improvements in cognitive functions (dppc2 0.35 for SCIP and 0.26 for FAB), with a positive correlation between SCIP score and the number of sessions attended (R = 0.86, p < 0.001), evident in the patients attending to at least 75 of the 100 walking sessions. Walking speed and VO2peak increased significantly and a decrease of body weight, BMI, systolic and diastolic blood pressure was also observed. The adherence to the walking program registered during Covid-19 period did not differ from that observed before the pandemic. The 12 CG (Control Group) patients maintaining the sedentary lifestyle did not display improvements of cognitive functions.

Conclusions

The main finding of this study is the improvement of cognitive functions which is significantly related to the number of walking sessions attended by participants with schizophrenia. The walking program, guided by exercise specialists, proved to be an enjoyable activity for people with mental disorder feasible even during the COVID-19 pandemic.

Trial registration Retrospectively registered on ISRCTN as non-randomized trial (n. ISRCTN14763786).
Osteosarcoma of the bladder: a case report
Authors: Oka Toshiki , Matsuzaki Kyosuke , Izumi Haruka , Nonomura Daichi , Mori Kiyoshi , Nishimura Kensaku
Published: March 2022

Background

Osteosarcoma arising from the bladder is extremely rare, with only 38 cases reported to our knowledge. It is often detected owing to hematuria, and is treated by surgery (for example, total cystectomy), radiation therapy, and chemotherapy; however, the prognosis is extremely poor.

Case presentation

An 83-year-old Japanese man underwent cystoscopy for postoperative follow-up of urothelial carcinoma of the bladder, which revealed a 2-cm nodular tumor on the right wall. He had a history of abdominal aortic aneurysm and hypertension, and had been smoking 15 cigarettes per day for 45 years. Seven years previously, the patient underwent transurethral resection of bladder tumor for a 5-cm tumor on the right wall of the bladder. The histopathological diagnosis was urothelial carcinoma. No recurrence had been detected since then. Transurethral resection of bladder tumor was performed, and the histopathological diagnosis was cystosarcoma. Because of his advanced age, we decided that it would be difficult to perform total cystectomy. We therefore performed a second transurethral resection of bladder tumor and found no residual tumor. At 29 months after surgery, the patient remains alive without recurrence.

Conclusion

Bladder osteosarcoma has a poor prognosis. However, our case was detected early, and treatment with transurethral resection of bladder tumor alone resulted in long-term survival without recurrence.
How big will the next eruption be?
Authors: Colosi Paul , Brodsky Emily E.
Published: March 2022

Anticipating the size of the next volcanic eruption in long-term forecasts is a major problem in both basic and applied volcanology. In this study, we investigate the extent to which eruption size is predictable based on historical and other attribute data. Data from the Smithsonian Global Volcanism Program (GVP) Catalog is used to determine the predictability of volcanic eruption size as quantified through the reported VEI (Volcano Explosivity Index). The numerical and categorical attributes from the global volcanic catalog were classified with trained random forest and simple prediction models to make a forecast of VEI that can be tested against the most recent eruption of each volcano. We compare these results to two different baseline predictability levels by: (a) selecting randomly from the global distribution of VEIs for the most recent eruptions to calculate a cohort baseline and (b) selecting the most frequent VEI for a given population to calculate a zero-rule baseline. We found that: (1) nearly any method that incorporates prior information on a specific volcano improves the prediction accuracy of the succeeding eruption VEI by at least 10 percentage points relative to the cohort baseline case, (2) incorporating attributes beyond previous VEIs can provide better accuracy and achieve up to 30 percentage point accuracy gains, (3) total accuracy of the VEI forecasting by these methods can be up to nearly 80% and (4) the zero-rule is an effective prediction method that is modestly outperformed (~ 5 percentage point gain) by random forest methods with multiple attributes on most datasets. We find no notable preference in accuracy based on volcano type. The results quantify the importance of volcano-specific information in long-term forecasting and may help practitioners assess their expected performance when anticipating future eruption size.
Physiology and metabonomics reveal differences in drought resistance among soybean varieties
Authors: Wang Xiyue , Li Yongping , Wang Xiaojing , Li Xiaomei , Dong Shoukun
Published: March 2022

Background

The soybean is an important food crop worldwide. Drought during the first pod stage significantly affects soybean yield, and understanding the metabolomic and physiological changes in soybeans under drought stress is crucial. This study identified the differential metabolites in initial pod stage soybean leaves under polyethylene glycol-simulated drought stress, using ultra performance liquid chromatography and tandem mass spectrometry, and the physiological indexes related to drought resistance.

Results

Physiologically, drought resistance also generates enzyme and antioxidant activity; levels of superoxide dismutase, peroxidase, and catalase first increased and subsequently decreased, while those of soluble sugar, soluble protein, malondialdehyde, and proline content increased in both varieties. The contents of CAT, proline and soluble sugar in Heinong 44 (HN44) were higher than those in Heinong 65 (HN65), and the contents of MDA were lower than those in HN65. In metabolomics, the OPLS-DA model was used to screen different metabolites. KEGG analysis showed that the two varieties resisted drought through different ways. Amino acid metabolism and lipid metabolism play a key role in drought resistance of the two varieties, respectively. TCA cycle was one of the core pathways of drought resistance in two varieties. Changes in the content of l-Asparagine and citric acid may be one of the reasons for the difference in drought resistance between the two varieties.

Conclusions

We think that the reasons of drought resistance among soybean varieties are as follows: the main metabolic pathways are different under drought stress; the contents of metabolites in these metabolic pathways are different; some physiological indexes are different, such as MDA, CAT, proline content and so on. Our study enhances the understanding of the metabolomic soybean drought stress response and provides a reference for soybean drought resistance breeding.
Coronavirus versus the textile industry: cluster lessons for future challenges
Authors: Puig Francisco , Cantarero Santiago , Verdone Francesco
Published: March 2022

Since the pandemic situation was officially declared, part of society was immersed in searching desperately for solutions to combat it. Textile firms addressed with uneven effectiveness the challenge of creating products that helped medical and civil professionals (e.g., personal protection equipment, masks, sanitary material, etc.). To do this, they had to face supply problems, lockdown, and make a significant innovative effort. This work aims to analyze the strategic response of the companies belonging to the Valencian Textile Cluster (VTC) (Spain) to the coronavirus crisis and the territorial factors that influenced it. We carried out a content analysis of the news in the main newspapers during February–July (2020). Our analysis revealed that, on average, VTC firms responded to the challenge more quickly and effectively than other Spanish textile firms. The most influential location-specific factors were the clustering developed, institutional support, and a deep-rooted tradition in producing technical-home textiles, although we also detected that social media collaborated in the process of transferring value information. The influence of all these factors was more intense in the epicenter of the cluster (Ontinyent). Consequently, our results highlight the cluster effect and offer lessons that can help manage unexpected future events more effectively.
A case of monosomy 21 presented with difficult tracheal intubation
Authors: Saito Yoshiki , Chaki Tomohiro , Nishihara Noriaki , Yamakage Michiaki
Published: March 2022

Background

Monosomy 21 is a rare chromosomal abnormality. It is mainly associated with mental retardation, intellectual disability, growth retardation, microcephaly, and characteristic facial features. General anesthesia in adults with this disease has not been reported. We report difficult airway management of an adult patient with monosomy 21.

Case description

A 30-year-old female was scheduled for laparoscopic gynecological surgery. She was diagnosed with monosomy 21 at birth and accompanied with mental retardation. Preoperative examination revealed limited mouth opening with Mallampati score of IV, but no abnormal laboratory test or chest X-P. Anesthesia was performed using general anesthesia with epidural analgesia. Although bag-mask ventilation was improved by a muscle relaxant, mouth opening was further restricted, and laryngoscope insertion was impossible. Tracheal intubation was achieved using a bronchofiberscope. The operation procedure was completed, and the patient was discharged from the hospital without any major postoperative complications.

Conclusions

In this patient, mouth opening was further reduced after induction of general anesthesia with a muscle relaxant. Preoperative evaluation and adequate preparation of airway management are important for general anesthesia in an adult patient with monosomy 21.
Randomized Trial of Osilodrostat for the Treatment of Cushing Disease
Authors: Gadelha Mônica , Bex Marie , Feelders Richard A , Heaney Anthony P , Auchus Richard J , Gilis-Januszewska Aleksandra , Witek Przemyslaw , Belaya Zhanna , Yu Yerong , Liao Zhihong , Ku Chih Hao Chen , Carvalho Davide , Roughton Michael , Wojna Judi , Pedroncelli Alberto M , Snyder Peter J
Published: March 2022

Context

Cushing disease, a chronic hypercortisolism disorder, is associated with considerable morbidity and mortality. Normalizing cortisol production is the primary treatment goal.

Objective

We aimed to evaluate the safety and efficacy of osilodrostat, a potent, orally available 11βhydroxylase inhibitor, compared with placebo in patients with Cushing disease.

Methods

LINC 4 was a phase III, multicenter trial comprising an initial 12-week, randomized, double-blind, placebo-controlled (osilodrostat:placebo, 2:1) period followed by a 36-week, open-label treatment period (NCT02697734). Adult patients (aged 18-75 years) with confirmed Cushing disease and mean urinary free cortisol (mUFC) excretion ≥ 1.3 times the upper limit of normal (ULN) were eligible. The primary endpoint was the proportion of randomized patients with mUFC ≤ ULN at week 12. The key secondary endpoint was the proportion achieving mUFC ≤ ULN at week 36 (after 24 weeks’ open-label osilodrostat).

Results

Seventy-three patients (median age, 39 years [range, 19-67]; mean/median mUFC, 3.1 × ULN/2.5 × ULN) received randomized treatment with osilodrostat (n = 48) or placebo (n = 25). At week 12, significantly more osilodrostat (77%) than placebo (8%) patients achieved mUFC ≤ ULN (odds ratio 43.4; 95% CI 7.1, 343.2; P < 0.0001). Response was maintained at week 36, when 81% (95% CI 69.9, 89.1) of all patients achieved mUFC ≤ ULN. The most common adverse events during the placebo-controlled period (osilodrostat vs placebo) were decreased appetite (37.5% vs 16.0%), arthralgia (35.4% vs 8.0%), and nausea (31.3% vs 12.0%).

Conclusion

Osilodrostat rapidly normalized mUFC excretion in most patients with Cushing disease and maintained this effect throughout the study. The safety profile was favorable.
A Cluster Randomized Noninferiority Field Trial of Gestational Diabetes Mellitus Screening
Authors: Ramezani Tehrani Fahimeh , Behboudi-Gandevani Samira , Farzadfar Farshad , Hosseinpanah Farhad , Hadaegh Farzad , Khalili Davood , Soleymani-Dodaran Masoud , Valizadeh Majid , Abedini Mehrandokht , Rahmati Maryam , Bidhendi Yarandi Razieh , Torkestani Farahnaz , Abdollahi Zahra , Bakhshandeh Marzieh , Zokaee Mehdi , Amiri Mina , Bidarpour Farzam , Javanbakht Mehdi , Nabipour Iraj , Nasli Esfahani Ensieh , Ostovar Afshin , Azizi Fereidoun
Published: March 2022

Context

Although it is well-acknowledged that gestational diabetes mellitus (GDM) is associated with the increased risks of adverse pregnancy outcomes, the optimal strategy for screening and diagnosis of GDM is still a matter of debate.

Objective

This study was conducted to demonstrate the noninferiority of less strict GDM screening criteria compared with the strict International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria with respect to maternal and neonatal outcomes.

Methods

A cluster randomized noninferiority field trial was conducted on 35 528 pregnant women; they were scheduled to have 2 phases of GDM screening based on 5 different prespecified protocols including fasting plasma glucose in the first trimester with threshold of 5.1 mmol/L (92 mg/dL) (protocols A, D) or 5.6 mmol/L (100 mg/dL) (protocols B, C, E) and either a 1-step (GDM is defined if one of the plasma glucose values is exceeded [protocol A and C] or 2 or more exceeded values are needed [protocol B]) or 2-step approach (protocols D, E) in the second trimester. Guidelines for treatment of GDM were consistent with all protocols. Primary outcomes of the study were the prevalence of macrosomia and primary cesarean section (CS). The null hypothesis that less strict protocols are inferior to protocol A (IADPSG) was tested with a noninferiority margin effect (odds ratio) of 1.7.

Results

The percentages of pregnant women diagnosed with GDM and assigned to protocols A, B, C, D, and E were 21.9%, 10.5%, 12.1%, 19.4%, and 8.1%, respectively. Intention-to-treat analyses satisfying the noninferiority of the less strict protocols of B, C, D, and E compared with protocol A. However, noninferiority was not shown for primary CS comparing protocol E with A. The odds ratios (95% CI) for macrosomia and CS were: B (1.01 [0.95-1.08]; 0.85 [0.56-1.28], C (1.03 [0.73-1.47]; 1.16 [0.88-1.51]), D (0.89 [0.68-1.17]; 0.94 [0.61-1.44]), and E (1.05 [0.65-1.69]; 1.33 [0.82-2.00]) vs A. There were no statistically significant differences in the adjusted odds of adverse pregnancy outcomes in the 2-step compared with the 1-step screening approaches, considering multiplicity adjustment.

Conclusions

The IADPSG GDM definition significantly increased the prevalence of GDM diagnosis. However, the less strict approaches were not inferior to other criteria in terms of adverse maternal and neonatal outcomes.
Endocrine-Disrupting Chemicals and Breast Cancer: Disparities in Exposure and Importance of Research Inclusivity
Authors: Santaliz Casiano Ashlie , Lee Annah , Teteh Dede , Madak Erdogan Zeynep , Treviño Lindsey
Published: March 2022

Endocrine-disrupting chemicals (EDCs) are known contributors to breast cancer development. Exposures to EDCs commonly occur through food packaging, cookware, fabrics, and personal care products, as well as external environmental sources. Increasing evidence highlights disparities in EDC exposure across racial/ethnic groups, yet breast cancer research continues to lack the inclusion necessary to positively impact treatment response and overall survival in socially disadvantaged populations. Additionally, the inequity in environmental exposures has yet to be remedied. Exposure to EDCs due to structural racism poses an unequivocal risk to marginalized communities. In this review, we summarize recent epidemiological and molecular studies on 2 lesser-studied EDCs, the per- and polyfluoroalkyl substances (PFAS) and the parabens, the health disparities that exist in EDC exposure between populations, and their association with breast carcinogenesis. We discuss the importance of understanding the relationship between EDC exposure and breast cancer development, particularly to promote efforts to mitigate exposures and improve breast cancer disparities in socially disadvantaged populations.
Estrogen Promotes Microvascularization in the Fetus and Thus Vascular Function and Insulin Sensitivity in Offspring
Authors: Albrecht Eugene D , Aberdeen Graham W , Babischkin Jeffery S , Prior Steven J , Lynch Terrie J , Baranyk Irene A , Pepe Gerald J
Published: March 2022

We have shown that normal weight offspring born to estrogen-deprived baboons exhibited insulin resistance, although liver and adipose function and insulin receptor and glucose transporter expression were unaltered. The blood microvessels have an important role in insulin action by delivering insulin and glucose to target cells. Although little is known about the regulation of microvessel development during fetal life, estrogen promotes capillary proliferation and vascular function in the adult. Therefore, we tested the hypothesis that estrogen promotes fetal microvessel development and thus vascular function and insulin sensitivity in offspring. Capillary/myofiber ratio was decreased 75% (P < 0.05) in skeletal muscle, a major insulin target tissue, of fetal baboons in which estradiol levels were depleted by administration of aromatase inhibitor letrozole. This was sustained after birth, resulting in a 50% reduction (P < 0.01) in microvessel expansion; 65% decrease (P < 0.01) in arterial flow-mediated dilation, indicative of vascular endothelial dysfunction; and 35% increase (P < 0.01) in blood pressure in offspring from estrogen-deprived baboons, changes prevented by letrozole and estradiol administration. Along with vascular dysfunction, peak insulin and glucose levels during a glucose tolerance test were greater (P < 0.05 to P < 0.01) and the homeostasis model of insulin resistance 2-fold higher (P < 0.01) in offspring of letrozole-treated than untreated animals, indicative of insulin resistance. This study makes the novel discovery that estrogen promotes microvascularization in the fetus and thus normal vascular development and function required for eliciting insulin sensitivity in offspring and that placental hormonal secretions, independent from improper fetal growth, are an important determinant of risk of developing insulin resistance.
Heterogeneity in Epinephrine Response to Experimental Hypoglycemia in Type 1 Diabetes and Controls
Authors: Zhang Yuan , Öz Gülin , Moheet Amir , Kumar Anjali , Alvear Alison , Mangia Silvia , Eberly Lynn , Seaquist Elizabeth R
Published: March 2022

Context

The epinephrine response (Epi) to a first episode of hypoglycemia (HG) has been proposed to be predictive of Epi in subsequent HG and to provide insight into the risk for developing HG-associated autonomic failure (HAAF) in healthy controls (HCs).

Objective

To determine if Epi and symptom response (SR) to the first episode of HG predicts who will develop HAAF after exposure to recurrent HG in volunteers with type 1 diabetes (T1D) and in HCs.

Design

Review of data collected between 2013 and 2019.

Setting

Academic clinical research unit.

Patients or Participants

Volunteers with T1D and HCs.

Interventions

Subjects participated in a preinduction protocol where they were exposed to three 2-hour episodes of clamped HG over 2 days. Data collected during clamp 1 were compared with data collected during clamp 3.

Main outcome measure

Difference in Epi and SR.

Results

Using the standard definition of HAAF in which HG-induced Epi during clamp 3 is at least 20% lower than during clamp 1, 21/28 HCs and 13/19 volunteers with T1D developed HAAF. Epi during clamp 1 was significantly higher in those subjects who developed HAAF than in those who did not in both groups (P = 0.02). If HAAF is defined as achieving a 20% reduction in HG-induced SR measured during clamp 3 compared with clamp 1, 10/27 HCs and 10/19 volunteers with T1D developed SR-based HAAF.

Conclusion

There was heterogeneity in the response to the preinduction protocol. Epi during clamp 1 was higher than in clamp 3 in HCs and in those with T1D who developed HAAF.
Muscle fat infiltration but not muscle cross-sectional area is independently associated with bone mineral density at the lumbar spine
Authors: Yang Qian , Yan Dong , Wang Ling , Li Kai , Liang Wei , Zhang Wei , Liu Yan Dong , Li Xiao Min , Blake Glen M , Konerth Natalie , Cheng Xiaoguang , Tian Wei , Hind Karen
Published: March 2022

Objective:

Although sarcopenia and osteoporosis are inter-related conditions that are common with advancing age, few studies have explored relationships between muscle quality and bone mineral density (BMD). We investigated age- and sex-specific paraspinal muscle fat infiltration (MFI), muscle cross-sectional area (CSA), and spine volumetric BMD (vBMD) in healthy Chinese adults.

Methods:

605 healthy adults aged 20–59 years (340 women, mean age 39.2 years; 265 men, mean age 38.8 years) had axial T  2WI MRI imaging of the lumbar spine and CSA (cm2) and MFI (%) were measured in the psoas and multifidus and erector spinae (MF-ES) muscles (L3–L4). MFI measurements were calibrated against a region of interest in an adjacent area of subcutaneous pure fat. L2–L4 vBMD was measured by quantitative CT. Age- and sex-specific subgroups were compared using the Mann–Whitney test. Multiple regression was used to test independent associations of MFI and CSA with vBMD.

Results:

Females had lower CSA and higher MFI than males in both the psoas and MF-ES muscles (p < 0.001). In females and males, MF-ES MFI increased with age (p < 0.001) and in females age-related increases were observed for the psoas muscles (p < 0.05). Greater fat infiltration of the MS-ES muscle unit was associated with lower vBMD in both sexes (p < 0.001) but not with CSA. Following adjustment for demographic variables and CSA, MS-ES MFI remained predictive of vBMD (β = −0.408 to −0.157, p < 0.001).

Conclusion:

We have demonstrated that, independent of CSA and demographic variables, MFI of the MF-ES muscles is predictive of lower lumbar spine vBMD in both sexes.

Advances in knowledge:

This is the first study to demonstrate that, independent of muscle size and demographic variables, MFI of the paraspinal MF-ES muscles is predictive of lower lumbar spine vBMD in both sexes.
The genome sequence of the grey top shell, Steromphala cineraria (Linnaeus, 1758)
Authors: Adkins Patrick , Mrowicki Robert , Harley Joanna , Mieszkowska Nova , Ferreira João G. R. N. ,   Marine Biological Association Genome Acquisition Lab,   Darwin Tree of Life Barcoding collective,   Wellcome Sanger Institute Tree of Life programme,   Wellcome Sanger Institute Scientific Operations: DNA Pipelines collective,   Tree of Life Core Informatics collective,   Darwin Tree of Life Consortium
Published: March 2022

We present a genome assembly from an individual Steromphala cineraria (the grey topshell; Mollusca; Gastropoda; Trochida; Trochidae). The genome sequence is 1,270 megabases in span. The majority of the assembly (99.23%) is scaffolded into 18 chromosomal pseudomolecules.
Ethnic differences in kidney function in childhood: the Born in Bradford Cohort Renal Study
Authors: Ziauddeen Nida , Jeffrey Robin F. , Waiblinger Dagmar , Fraser Simon D.S. , Alwan Nisreen A. , Yuen Ho M. , Azad Rafaq , Mason Dan , Wright John , Coward Richard J.M. , Roderick Paul J.
Published: March 2022

Background: Endstage kidney failure rates are higher in South Asians than in White Europeans. Low birth weight is associated with adult chronic kidney disease and is more common in South Asians. Foetal kidney size was smaller in South Asians in the Born in Bradford (BiB) birth cohort. As part of BiB follow up, we aimed to investigate if there were ethnic differences in kidney function and blood pressure in early childhood and whether this was mediated by foetal kidney size.

Methods: Serum creatinine, cystatin C, urea, and urinary albumin to creatinine ratio (ACR), protein to creatinine ratio (PCR) and retinol binding protein (RBP) were analysed in blood and urine samples from those who participated in the BiB follow-up at 7-11 years. Ethnicity was categorised by parental self-report as White European and South Asian. Estimated glomerular filtration rate (eGFR) was calculated using Schwartz, and cystatin C Zappitelli and Filler equations. Linear regression was used to examine the association between ethnicity and eGFR, PCR and blood pressure.

Results: 1591 children provided blood (n=1403) or urine (n=625) samples. Mean eGFR was 92 ml/min/1.73m2 (standard deviation (SD) 9) using Schwartz (n=1156) and 94 (SD 11) using Zappitelli (n=1257). CKD prevalence was rare (1 with eGFR <60 ml/min/1.73m2, 14 (2.4%) had raised ACR (>2.5 mg/mmol in boys/3.5 mg/mmol in girls). Diastolic blood pressure was higher in South Asian children (difference 2.04 mmHg, 95% CI 0.99 to 3.10) but was not significant in adjusted analysis. There was no evidence of association in adjusted models between ethnicity and any eGFR or urinary measure at this age.

Conclusions: There was no evidence of significant ethnic differences in kidney function at pre-pubertal age despite differences in kidney volume at birth. Longitudinal follow-up is required to track ethnic patterns in kidney function and blood pressure as children develop through puberty.