bluuebunny/crossref_metadata_2025_split huggingface dataset:
PSAT047 Dual Heterozygous Mutations in CYP21A2 and CYP11B1 in a Case of Nonclassic Congenital Adrenal Hyperplasia
Authors: Frontera Eric , Brown Joshua J , Ghareebian Hagop , Mariash Cary 
Published: November 2022

Abstract

Background
Congenital Adrenal Hyperplasia (CAH) is classically attributed to defective 21-hydroxylase, caused by mutations in CYP21A2, impairing the production of mineralocorticoids and glucocorticoids and subsequently shifting steroidogenesis towards androgen production. This produces a classic constellation of neonatal symptoms, including genital virilization, salt-wasting, and adrenal crisis. A rare cause of CAH is a defect in 11β-hydroxylase from a mutation in CYP11B1, preventing production of cortisol and corticosterone, resulting in hypertension, hypokalemia, and androgen excess. Reports of combined mutations in CYP21A2 and CYP11B1 in the literature and the clinical manifestations of such a case are not well described. Here we present a case report wherein a pair of heterogenous mutations in CYP2A12 and CYP11B1 were detected in a new diagnosis of nonclassic Congenital Adrenal Hyperplasia, including a previously undescribed mutation in CYP11B1.

Clinical Case
The patient is a 30-year-old female who presented to her primary care clinic with teenage-onset irregular menses occurring every 2-3 months. She also reported hirsutism, but never had acne, changes in thirst or urination, or breast discharge. Primary evaluation revealed prolactin of 34.7 ng/mL, prompting a pituitary MRI which revealed a 2×3mm lesion. At this point, referral was made to endocrinology for endocrinological. PCOS was felt to be the top differential for her hirsutism and irregular menses but further workup to rule out CAH revealed a 17-OH-Progesterone of 554 ng/dL and a Testosterone of 83 ng/dL. Subsequently, a 250 mcg cosyntropin test increased 17-OH progesterone to 837 ng/dL and resulted in a cortisol of 24.7 mCg/dL after 60 minutes. Subsequent CAH gene sequencing was performed and revealed a heterogeneous pathogenic CYP21A2 variant (c.332_339 del; p.Gly111Valfs*21) and a heterogeneous previously undescribed variant of undetermined significance in CYP11B1 (c.1123C&gt;T; p.Leu375Phe).

Conclusion
At least 100 mutations of CYP11B1 have been found to cause CAH due to 11β-Hydroxylase deficiency. Our case adds to the growing database of described mutations in CY11B1 and suggests that heterogenous mutations in two different genes may present phenotypically as nonclassic CAH in a potentially epistatic fashion. This enriches earlier conclusions that broader genetic analysis beyond CYP21A2 deletions is needed to identify the genotypes of those with CAH due to the complex diversity of genetic mutations, and ought to remind clinicians to consider it as a diagnosis, particularly in young women whose hyperandrogenism or menstrual irregularities cannot be explained by common endocrinological abnormalities or do not have an appropriate response to traditional treatment.
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
RF17 | PMON24 The paradox of combined pituitary hormone deficiency and tall stature: a glimpse from exome sequencing
Authors: Carvalho Luciani R , Benedetti Anna Flãvia , Oliveira Julia 
Published: November 2022

Abstract

Introduction
An intact GH-IGF-1 axis is known to be essential for proper growth. However, cases in which individuals with growth hormone deficiency (GHD) reach target height without the use of GH suggest that other mechanisms may play a role in the growth process. Out of 209 patients with hypopituitarism followed in the endocrinology clinic at HCFMUSP, 9 presented with normal stature despite GHD and hypogonadotropic hypogonadism. Among them, 1 male patient presented with tall stature. The mechanisms under growth without growth hormone are poorly understood, so we hypothesized that genetic mutations in genes related to tall stature could be a plausible explanation. The aim of the present work was to look for allelic variants in the exome that could be associated with tall stature, combined pituitary hormone deficiency and/or skeletal deformities. The index male patient presented at the age of 28 to a medical assistance due to the lack of pubertal development, leading to the diagnosis of FSH/LH and TSH deficiencies and thus treated accordingly. He was still growing even under testosterone replacement and noticed that his hand and fingers also got bigger in this period. At 32-year-old he presented to our service with a stature of 193.5cm (z score of +2.40) being out of his target height range. An arm span of 195cm was notice together with skeletal deformities such as claw toes, trigger fingers in hands and a barrel chest. At this time ACTH and GH deficiencies were diagnosed and an adult dose of GH was initiated. Over one year treatment he grew 1 cm even presenting complete closed epiphyses in hands but incomplete epiphyseal fusion in the iliac crest (Risser 4). In the skeletal X ray scoliosis, deformities in hands and feet were noticed. Pituitary MRI revealed an ectopic neurohypophysis and a reduced adenohypophysis. Whole exome sequencing was performed and allelic variants in exonic or splice site regions with frequency of less than 1% were prioritized. Out of 26 variants, 13 were classified as VUS or pathogenic in the genes PSG4, ZGPAT, LRP2, LRP5, LRP6, RYR1, REL SPAST, SDHC, EGFR, ARID3B and TGFB2, being the last 5 genes never described in 4 different populational databases (gnomAD, 1000G, ABraOM and SELAdb). Allelic variant in TGFB2 gene has been related to Marfan syndrome. Family members are having these genes in the process of being segregated.

Conclusion
Mutations in genes related to tall stature may be a mechanism that could explains normal growth among individuals with GHD.
Presentation: Sunday, June 12, 2022 12:42 p.m. - 12:47 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
LBODP071 Early Detection Of Immune-mediated Hypophysitis With Use Of Checkpoint Inhibitor Immunotherapy
Authors: Lai William , Naidoo Shiva , Yossef Kristena 
Published: November 2022

Abstract
Hypophysitis is an inflammatory infiltration of the pituitary gland. Association with cytotoxic T-lymphocyte antigen 4 (CTLA-4) targeting was described with a recommendation of discontinuing the treatment in such conditions . Hypophysitis has become more prevalent with increased use of immune checkpoint inhibitors with late detection being associated with a high morbidity and mortality. Symptomatic presentation, along with hemodynamic and serum abnormalities warrant urgent intervention as early measures prevent progression. This case is about a 60-year-old female with metastatic renal clear cell carcinoma status post right radical nephrectomy on combined nivolumab and ipilimumab (NIVO/IPI) and history notable for persistent atrial fibrillation on warfarin presented to the hospital after a fall. Eight days after her second cycle on NIVO/IPI, the patient developed hot flashes, vomiting, weakness, and vertiginous symptoms. Her exam was notable for atrial fibrillation with rapid ventricular rate and hypotension. Serology was notable for a sodium of 119 mEq/mL, prompting admission to the hospital. Due to high clinical suspicion for hypophysitis based on serological findings, the patient was given a dose of methylprednisolone then daily hydrocortisone to reverse the pituitary inflammation. Fludrocortisone was started for adrenal insufficiency. MRI of the brain with IV contrast was notable for abnormal enhancement and thickening of the pituitary stalk concerning for hypophysitis. The patient clinically improved with resolution of her dizziness, hot flashes, and vomiting. Her serum sodium improving to 132 mEq/mL. She was discharged home with immunotherapy held. Hypophysitis is a rare inflammatory disease affecting 1 in 7 million. Typical symptoms include headache, vision changes, fatigue, and hypopituitary deficiencies. Reported immunotherapies with incidences of secondary hypophysitis include CTLA-4 and PD-1 therapeutics. Immunotherapy associated hypophysitis occurs in &lt;7% of patients. Hypophysitis is diagnosed by laboratory findings and imaging which can identify this acute process via enhancement and swelling of the pituitary gland . Management modalities include surgery, anti-inflammatory therapy, and conservative therapy. Medical management is mainly directed at the correction of pituitary hormone deficiencies and reduction of pituitary inflammation using glucocorticoid therapy .
Presentation: No date and time listed
LBODP073 Non-functioning Pituitary Macroadenoma Presenting As Osteopenia In A Male
Authors: Parihar Aisha , Patel Amani , Patel Alpa 
Published: November 2022

Abstract
Non-functioning pituitary macroadenomas (NFPAs) account for 14-54% of all pituitary adenomas. NFPAs are benign, but mass effects may lead to significant symptoms, including visual impairment and pituitary insufficiency, of which secondary hypogonadism is present in 75% of reported cases. Patients with hypogonadism may experience decreased bone density, libido, muscle mass/strength, and fatigue. We describe a patient who presented with osteopenia, in addition to atypical symptoms of secondary hypogonadism, associated with low testosterone levels. Further workup disclosed a large pituitary macroadenoma. A 56-year-old male presented to the clinic for a two-year history of diffuse joint pain. X-rays were significant for bone loss. This led to a bone density scan that showed osteopenia with a T score of -2.3 in the lumbar spine and left femoral neck. He had no prior history of fractures or loss in height. Risk factors for bone disease were only pertinent for history of osteoporosis in his mother. He was referred to endocrinology for further evaluation. Work up included normal vitamin D levels, 24-hour urine calcium excretion, morning cortisol, and TSH. Given the patient's osteopenia and additional complaints of decreased appetite, weight loss, fatigue, and muscle weakness, testosterone levels were checked and found to be low. Free testosterone level was 14.3 pg/ml with inappropriately low FSH and LH. Prolactin was normal at 12.5 ng/ml. He subsequently had an MRI brain which revealed a pituitary macroadenoma measuring 2. 0×2.4×2.4 cm with mass effect on the optic chiasm. However, the patient did not complain of headaches or visual disturbances and visual field testing was normal. He underwent transsphenoidal resection of the pituitary tumor which led to normalization of testosterone levels and resolution of all his symptoms. This case exemplifies how non-specific symptoms of hypogonadism and absence of mass effect symptoms can lead to a delay in diagnosis of NFPA. Typically, NFPAs are detected when they are large enough to cause symptoms of mass effect which, interestingly, were absent in this patient despite compression of the optic chiasm. Male hypogonadism increases the risk for bone disease. Thus, it is important to pursue work up for secondary hypogonadism in males presenting with osteopenia/osteoporosis despite lack of overt symptoms. A thorough history and workup are essential in diagnosing NFPA. Prompt detection of NFPA can facilitate timely management leading to clinical improvement. The first line of treatment for NFPAs causing neurological symptoms is transsphenoidal surgical resection. Surgery is also recommended for NFPAs that are at high risk for causing visual deficits due to involvement of optic chiasm, as was seen in this patient. Post-surgical follow up includes long-term routine monitoring of hormone levels and neuroimaging.
Presentation: No date and time listed
Effect of Ice Slush on Reducing the Oculocardiac Reflex During Strabismus Surgery
Authors: Qi Xin , Zou Fei , Wei Xin , Wu Ying , Cao Lijun , Xu Junmei , Cui Yulong 
Published: November 2022

BACKGROUND:
The aim of this study was to explore whether ice slush (IS) causing local hypothermia can effectively inhibit the oculocardiac reflex (OCR) during strabismus surgery.

METHODS:
This prospective, randomized, double-blind study included 58 patients with concomitant strabismus scheduled for lateral rectus (LR) recession under general anesthesia. Patients were randomly allocated to receive IS (IS group) or standard treatment (control group) with sterile saline at room temperature before surgery. OCR was defined as a sudden decrease in heart rate (HR) of >15% from baseline. If one incidence of the OCR was found in 1 patient in any stage (0/I/II/III), the patient was defined as an OCR responder, and the incidence of overall OCR was the incidence of OCR responders. The primary outcome was the incidence of overall OCR during all stages of the surgery, which was analyzed by the Z test and computed based on the absolute risk difference with 2-sided 95% confidence intervals (CIs) using the Newcombe method.

RESULTS:
The overall OCR occurred in 19 of 29 patients (62.5% [95% CI, 45.7–82.1]) in the IS group and 28 of 29 patients (96.6% [95% CI, 82.2–99.9]) in the control group (absolute risk difference, −31.0% [95% CI, −49.4 to −11.0]; Z test, P < .001), which demonstrated that the incidence of overall OCR in IS group was significantly lower than that in the control group.

CONCLUSIONS:
IS on the ocular surface causing local hypothermia is a promising and easily accessible method to reduce the overall OCR, which can improve the safety of strabismus surgery.
Deep Brain Stimulation and Responsive Neurostimulation Implantation for Medically Refractory Epilepsy: A Case Report Study of a Single-Center's Experience
Authors: Restrepo Andres F. , Zillgitt Andrew , Burdette David E. , Ali Rushna 
Published: November 2022

BACKGROUND AND IMPORTANCE:
Nearly 25% of all epilepsy is drug-resistant epilepsy. Responsive neurostimulation (RNS) and deep brain stimulation (DBS) offer viable options when resection or ablation is not feasible. Neuromodulation leads to improved seizure control. However, in patients with highly complex epileptogenic networks, a multimodality approach using simultaneous RNS and DBS may provide a summative benefit.

CLINICAL PRESENTATION:
We present 2 cases of drug-resistant epilepsy who received simultaneous anterior nucleus of the thalamus DBS and RNS neuromodulation. To our knowledge, this is the first report of simultaneous DBS and RNS neurostimulation for the treatment of epilepsy. Given the complexity of their seizure networks, a combined neuromodulatory approach was deemed best to achieve seizure control. Both experienced multiple seizure semiology patterns consistent with multifocal onsets which were confirmed on phase I monitoring, nuclear medicine, and magnetoencephalography studies. Case 1 had a seizure reduction of 75% to 89% at 12 months which has remained stable at last follow-up (26 months) and case 2 achieved near seizure freedom and remained seizure-free at last follow-up (16 months).

CONCLUSION:
Neuromodulation has proven efficacious and safe in randomized controlled trials for the treatment of epilepsy. This is particularly important in multifocal epilepsy or if resective surgery is not an option. The optimal stimulation pathways and multimodal neuromodulation technique remains under investigation. We are the first to report that RNS and DBS implantation in the same patient is feasible, without major adverse effects and potentially effective.
Comparison of sleep and health behaviours among people with diabetes and a nondiabetic group in Phitsanulok, Thailand: a cross-sectional study
Authors: Juntarawijit Chudchawal , Juntarawijit Yuwayong 
Published: November 2022

Background: Type 2 diabetes mellitus (T2DM) is a global public health problem. To avoid disease complications, people with diabetes have to control their blood glucose and maintain a healthy lifestyle including a healthy diet, weight control, moderate exercise, and smoking cessation. Methods: This study aimed to survey sleep, eating, and exercise behaviours of people with diabetes in the Bang Rakam district, a rural community in Phitsanulok province, Thailand. The data on sleep and other health behaviours were taken from 1,385 T2DM patients and 1,394 non-T2DM controls, who were aged 30 - 85 years and were free from other chronic diseases. The data were collected using a structured questionnaire. Results: Compared to the control group, the people with diabetes had a significantly higher body mass index (BMI). However, only a few of them smoke cigarettes and drink alcohol. Most of the participants were ‘morning people’ who slept 7-9 hours per day. It was found that sleep ≥8 hours increased the risk of diabetes among women (OR = 1.27, 95% CI 1.03 - 1.56). The people with diabetes also reported eating chicken and vegetables more than the control group. They also avoided eating beef and eating more than a cup of rice per meal. However, the T2DM group did fewer physical activities, such as walking, biking, or playing sports, during their leisure time. Conclusions: Most people with diabetes (T2DM) in a rural community of Thailand had healthy behaviours regarding sleep duration, sleep pattern, lifestyle, eating, smoking and alcohol consumption, except exercise and physical activity. The findings here contrast with the common perception that people with diabetes have bad lifestyle patterns, instead it showed that a healthy lifestyle pattern based on dietary patterns alone may not be sufficient and that lifestyle prevention of diabetes should always include physical activity as an integral part.
Effectiveness of antepartum breathing exercises on the outcome of labour: A randomized controlled trial
Authors: Karkada Sushmitha R , Noronha Judith A , Bhat Shashikala K , Bhat Parvati , Nayak Baby S 
Published: November 2022

Abstract Background Childbirth is a life-transforming intense event to a woman and her family. Even though a variety of non-pharmacological techniques are readily available to alleviate the distress of women in labour, the majority of women are unaware of its benefits. The objective of the study was to explore the impact of a simple non-pharmacological technique i.e., antepartum breathing exercises on maternal outcomes of labour among primigravid women. Methods A single centre prospective, single-blinded, randomized controlled trial was conducted at the antenatal outpatient clinic of a secondary healthcare institution. Eligible primigravid women were randomized into intervention and standard care groups. Both groups received standard obstetrical care. In addition, the intervention group were taught antepartum breathing exercises and were advised to practise daily and also during the active stage of labour. The primary outcome of the trial was the maternal outcome of labour measured in terms of onset of labour, nature of delivery, duration of labour, and need for augmentation of labour. Data was collected using World Health Organization (WHO) partograph, structured observational record on the outcome of labour. Results A total of 98 (70%) primigravid women who practised antepartum breathing exercises had spontaneous onset of labour. The odds of spontaneous onset of labour after randomization in the intervention group was 2.192 times more when compared to standard care at a (95% confidence interval 1.31–3.36, p<.001). Also, the requirement for augmentation of labour was minimal and there was a reduction in the rate of caesarean deliveries (p <.05) based on the χ2 test. The overall mean duration of labour was less compared to standard care group F(1)= 133.800, p <.001. Conclusion Antepartum breathing exercises during labour can facilitate spontaneous vaginal birth, shorten the duration of labour, and reduce the need for operative interference.
So, Who Likes You? Evidence from a Randomized Field Experiment
Authors: Bapna Ravi , McFowland Edward , Mojumder Probal , Ramaprasad Jui , Umyarov Akhmed 
Published: November 2022

With one-third of marriages in the United States beginning online, online dating platforms have become important curators of the modern social fabric. Prior work on online dating has elicited two critical frictions in the heterosexual dating market. Women, governed by age-old social norms of not making the first move, are inhibited in their interactions in that they do not initiate contact with men. On the other side, men send an abundance of messages, the majority of which do not convert to matches. A key distinguishing feature of online dating versus its traditional counterpart is the ability to leave a range of digital signals not replicable in the offline world. These digital signals can impact the nature of online dating platform outcomes. In this paper, we study the impact of a feature that reveals “who likes you” (WLY) on engagement, the number of matches, match efficiency, and match sorting in online dating. This feature reveals the identity of the voters who have rated the focal user with a like. To causally identify the effect of this feature, we conduct a large-scale randomized control trial in collaboration with a major North American dating platform. The treatment causes women to be more proactive, sending 7.4% more messages, which is a highly desirable market improvement given that men send double the number of messages compared with women. Further, we find that the women endowed with this feature increase their matches by 14.4%, whereas men increase their matches by 11.5%. Analyzing the moderating impact of desirability—a key aspect of the WLY feature—provides us with nuanced findings. Depending on the levels of each of the two parties’ desirability, we see evidence of sorting, encouragement, and discouragement. This paper was accepted by Anandhi Bharadwaj, information systems. Supplemental Material: The Online Appendix is available at https://doi.org/10.1287/mnsc.2022.4576 .
Validity and reliability of the Indonesian version of the new brief job stress questionnaire (short version) for work-related stress screening among office workers
Authors: Adi Nuri Purwito , Da Lopez Ansgar Azurit Virenti Paska , Diatri Hervita , Werdhani Retno Asti , Soemarko Dewi Sumaryani , Fitriani Dewi Yunia 
Published: November 2022

BACKGROUND The short version of the new brief job stress questionnaire (SV-NBJSQ) that is originally in Japanese could evaluate work-related stress in Indonesian office workers. However, it has not been validated in Indonesian. Thus, this study aimed to test the validity and reliability of the Indonesian version of the SV-NBJSQ.
METHODS This study was conducted by linguistic and cultural adaptation of the original Japanese questionnaire into Indonesian and continued with exploratory factor analysis, internal consistency, and reliability test of Cronbach’s alpha. Electronic and paper-based data were collected using total sampling from office workers at two companies in Jakarta from December 2017 to August 2018.
RESULTS A total of 438 respondents filled the questionnaire. The final version of the questionnaire consisted of 63 items, screened based on a loading factor of >0.4 and 13 factors (dimensions). Each factor had a Cronbach’s alpha of 0.628–0.887, while the entire 63 had 0.904 with a total documented cumulative variation of 64.97%.
CONCLUSIONS The Indonesian version of the SV-NBJSQ is valid and reliable. Thus, we may use it as a more suitable, updated, and comprehensive tool to evaluate work-related stress among office workers.
Out-of-plane displacement sensor based on the Talbot effect in angular-modulated double-layer optical gratings
Authors: Cao Bin , Zhang Rui , Niu Qianqi , Ma Xiaochen , Yang Zhiyong , Li Mengwei , Xin Chenguang 
Published: November 2022

Based on the Talbot effect of optical gratings, we propose a novel
out-of-plane optical displacement sensor with an ultracompact
structure, to the best of our knowledge. Using two optical gratings
with a slight angle between them, two angular-modulated signals with a
phase difference of 90° are obtained associated with a two-quadrant
photodetector, which are in sinusoidal relationship with the
displacement in the direction perpendicular to the grating plane.
Using an interpolation subdivision circuit with a subdivision factor
of 1000, out-of-plane displacement measurement with a resolution of
11.23 nm within a range of 1 mm is obtained.