bluuebunny/crossref_metadata_2025_split huggingface dataset:
Appropriate Statistical Methods to Assess Cross-study Diagnostic 23-Gene Expression Profile Test Performance for Cutaneous Melanocytic Neoplasms
Authors: Goldberg Matthew S. , Cockerell Clay J. , Rogers Jason H. , Siegel Jennifer J. , Russell Brooke H. , Hosler Gregory A. , Marks Etan 
Published: August 2024

Abstract:
Comparing studies of molecular ancillary diagnostic tests for difficult-to-diagnose cutaneous melanocytic neoplasms presents a methodological challenge, given the disparate ways accuracy metrics are calculated. A recent report by Boothby-Shoemaker et al investigating the real-world accuracy of the 23-gene expression profile (23-GEP) test highlights this methodological difficulty, reporting lower accuracy than previously observed. However, their calculation method—with indeterminate test results defined as either false positive or false negative—was different than those used in previous studies. We corrected for these differences and recalculated their reported accuracy metrics in the same manner as the previous studies to enable appropriate comparison with previously published reports. This corrected analysis showed a sensitivity of 92.1% (95% confidence interval [CI], 82.1%–100%) and specificity of 94.4% (91.6%–96.9%). We then compared these results directly to previous studies with >25 benign and >25 malignant cases with outcomes and/or concordant histopathological diagnosis by ≥3 dermatopathologists. All studies assessed had enrollment imbalances of benign versus malignant patients (0.8–7.0 ratio), so balanced cohorts were resampled according to the lowest common denominator to calculate point estimates and CIs for accuracy metrics. Overall, we found no statistically significant differences in the ranges of 23-GEP sensitivity, 90.4%–96.3% (95% CI, 80.8%–100%), specificity, 87.3%–96.2% (78.2%–100%), positive predictive value, 88.5%–96.1% (81.5%–100%), or negative predictive value, 91.1%–96.3% (83.6%–100%) between previous studies and the cohort from Boothby-Shoemaker et al with this unified methodological approach. Rigorous standardization of calculation methods is necessary when the goal is direct cross-study comparability.
Metastatic Adrenocortical Carcinoma to the Skin: A Case Report and Review of This Unusual Neoplasm
Authors: Lee-Diaz Efrain , Contreras Carlo , Plaza Jose A. 
Published: August 2024

Abstract:
Adrenocortical carcinoma is a very rare oncologic condition with poor prognosis that usually metastasizes to the lungs, liver, local lymph nodes, and peritoneum at initial presentation. However, skin metastasis is very uncommon and has rarely been reported even in advanced stages of the disease. We present a case of a 41-year-old man with a known history of adrenocortical carcinoma of the right adrenal gland that presented with an arm mass. The histopathologic sections showed a multinodular necrotic malignant neoplasm in dermis and subcutaneous fat composed of atypical epithelioid cells with ample granular cytoplasm and pleomorphic vesicular nuclei with frequent intranuclear inclusions and atypical mitoses. The immunohistochemical stains showed tumor cells that were strongly positive for synaptophysin and inhibin, only focally positive for Melan-A, and negative for AE1/AE3. The histopathologic features and the immunohistochemical profile confirmed the diagnosis of metastatic carcinoma consistent with adrenal cortical origin. The diagnosis can be difficult (especially when no clinical data are provided), and an immunohistochemical battery is often useful in distinguishing this tumor from other tumors with similar cytomorphological features.
Anetoderma in the Setting of a Hematologic Abnormality and COVID-19 Infection
Authors: Xu Kathryn K. , Proffer Sydney L. , Torgerson Rochelle R. , Peters Margot S. 
Published: August 2024

Abstract:
Anetoderma is an uncommonly reported dermatosis clinically characterized by discrete skin lesions resulting from elastic fiber loss within the dermis. Although primary anetoderma has been considered idiopathic, a range of associated disorders, particularly prothrombotic abnormalities, have been reported. We present a 79-year-old woman with a heterozygous Factor V Leiden mutation who developed anetoderma shortly after COVID-19 infection complicated by a thromboembolic event. Our patient adds to the literature on the occurrence of anetoderma in the setting of infection and/or a prothrombotic disorder.
Examining How National Levels of Life Expectancy, Education, and Income Influence Early Childhood Development: The Mediating Role of the Child's Nurturing Context
Authors: Rothenberg W. Andrew , Bornstein Marc H. , Putnick Diane L. , Lansford Jennifer E. 
Published: August 2024

ABSTRACT:

Objective:
Forty-three percent of children younger than 5 years in low- and middle-income countries (LMICs) are at risk of not meeting their developmental potential. This study investigated how 3 aspects of national development (national life expectancy, education, and income levels) are associated with early childhood development by influencing 5 domains of nurturing care (caregiving, the learning environment, safety and security, nutrition, and the health of the home environment).

Methods:
In total, 159,959 families with children aged 36 to 59 months living in 51 LMICs provided data. National development was measured using 3 indicators (national life expectancy, education, and income levels), and nurturing care was measured using 10 indicators that collectively captured the 5 nurturing care domains. Path analyses examined how nurturing care indicators mediated the effects of national development on early childhood development.

Results:
Higher national life expectancy was directly associated with more advanced childhood development. Higher national levels of education and income were indirectly associated with more advanced childhood development through aspects of nurturing care, such as reduced caregiver psychological aggression or physical violence, increased learning materials and wired appliances in the home environment, and greater caregiver education and child height-for-age. Greater caregiver cognitive caregiving practices promoted childhood development, regardless of levels of national development.

Conclusion:
Intervening to promote caregiver education, appropriate discipline strategies, cognitive caregiving practices, and family access to wired appliances, learning materials, and adequate nutrition is key to promoting childhood development in nations with lower levels of national development.
DYNAMIC VIRAL LOAD MONITORING AND METAGENOMIC SEQUENCING IN ACUTE RETINAL NECROSIS CAUSED BY VARICELLA-ZOSTER VIRUS
Authors: Gu Junxiang , Lei Boya , Wang Zhujian , Zhang Ting , Jiang Tingting , Zhang Peijun , Chen Wenwen , Zhang Yanqiong , Jiang Rui , Xu Gezhi , Chang Qing , Zhou Min 
Published: August 2024

Purpose:
To analyze the trend of intraocular viral load after antiviral treatment in patients with varicella-zoster virus–induced acute retinal necrosis and to explore the effect of viral genotypes on clinical manifestations.

Methods:
In this case series, viral load was detected using polymerase chain reaction from aqueous humor during treatment; viral load curves were fitted, and the time required to reach the inflection point between plateau phase and logarithmic reduction phase was estimated. Variations in viral genomes were detected by metagenomic sequencing.

Results:
Twenty eyes of 20 patients were included. The median (interquartile range) initial viral load was 5.9 × 107 (1.1 × 107–1.1 × 108) copies/mL. The average duration of retinitis was 5 ± 3 weeks. The average time required to reach the inflection point was 4.2 ± 1.6 days. Time required to reach the inflection point was correlated with the duration of retinitis (P = 0.025). Patients with varicella-zoster virus carrying the p.S715* variation in ribonucleotide reductase (RNR) subunit 1 gene had lower initial viral loads (median 1.3 × 107 copies/mL) than those without (median 1.1 × 108 copies/mL; adjusted P = 0.030).

Conclusions:
The inflection of viral load curve is helpful to estimate the length of plateau phase and the duration of retinitis during antiviral treatment in patients with acute retinal necrosis. Loss-of-function variation in RNR gene might be correlated with lower virulence of varicella-zoster virus.
Progressive Paracentral Visual Field Loss at Low Intraocular Pressures Following LASIK
Authors: Kaplan Tyler M. , Sit Arthur J. , Patel Sanjay V. , Roddy Gavin W. 
Published: August 2024

Intraocular pressure is currently the only known reliable, modifiable risk factor for the development and progression of glaucoma. Other risk factors for glaucoma include increasing age, myopia, decreased central corneal thickness, and low corneal hysteresis (CH) measurements. Photoablative keratorefractive surgery including laser assisted in situ keratomileusis (LASIK) has become a common way to treat refractive error, with over 25 million procedures performed in the United States alone. Though myopic LASIK has been associated with a decrease in CH measurements, relatively little is known about the risk of LASIK on glaucoma onset and progression. Here we present an observational study of 4 consecutive relatively young and otherwise healthy glaucoma patients with a history of myopic LASIK who showed progression of paracentral visual field deficits at intraocular pressures of 12 mm Hg or less while being carefully monitored. Therefore, these patients required lower targets of intraocular pressure, in the single-digit range, to slow or halt progression. In this cohort, the average corneal hysteresis was more than 2 standard deviations below normal values. This series suggests that additional study into the association of LASIK and glaucoma is warranted, including the potential risk contribution of diminished CH. These studies may be particularly relevant as patients who underwent LASIK procedures in the early 2000s may now be at increased risk of glaucoma due to the risk factor of age.
Peripapillary and Macular Vessel Density in Unilateral Early Pseudoexfoliation Glaucoma
Authors: Solmaz Nilgun , Oba Turker 
Published: August 2024

Précis:
In early pseudoexfoliation glaucoma (PXG), radial peripapillary capillary vessel density (RPC-VD) was reduced nasally, while the retinal nerve fiber layer (RNFL) thinned from the nasal to temporal sectors. Nonglaucomatous fellow eyes demonstrated no RPC-VD or RNFL loss in comparison to the controls.

Purpose:
To evaluate peripapillary and macular vessel density (VD) in unilateral early PXG and unaffected fellow eyes compared with healthy controls.

Methods:
This cross-sectional study included 28 eyes with PXG and 28 nonglaucomatous, pseudoexfoliation-free fellow eyes of 28 patients, and 28 eyes of 28 healthy participants. All subjects underwent optical coherence tomography angiography (OCTA) imaging. RPC-VD, macular VD, retinal nerve fiber layer (RNFL) thickness, and ganglion cell complex (GCC) thickness were compared among the groups.

Results:
The average RPC-VD and RNFL thickness were significantly reduced in PXG eyes compared with both fellow eyes and the control group (P<0.001–0.002). In fellow eyes, neither RNFL thickness nor RPC-VD parameters differed from controls. In sector-based analysis, RPC-VD loss in the PXG eyes was significant in the nasal-superior, nasal-inferior, superonasal, and inferonasal sectors (P=0.005–0.031), while RNFL thinning extended from the nasal sectors toward the superotemporal and temporal-superior sectors (P<0.001–0.014). RPC-VD was strongly correlated with average and all sector RNFL thicknesses (r=0.402–0.759, P<0.001–0.034). While perifoveal GCC differed from both fellow and control eyes (P<0.001), there was no significant difference in macular VD parameters among the groups. RPC-VD and RNFL had comparable area under receiver operating curve (AUROC) values in the average and nasal sectors, while RPC-VD had no ability to distinguish PXG from controls in the superotemporal and inferotemporal sectors.

Conclusion:
In the early stages of PXG, RNFL parameters mostly appear to have better diagnostic ability than RPC-VD parameters. Fellow eyes in the preclinical stage may not exhibit any RPC-VD and RNFL loss detectable by current OCTA technology.
Visualizing the modulation of neurokinin 1 receptor–positive neurons in the superficial dorsal horn by spinal cord stimulation in vivo
Authors: Xu Qian , Zheng Qin , Cui Xiang , Cleland Andrew , Hincapie Juan , Raja Srinivasa N. , Dong Xinzhong , Guan Yun 
Published: August 2024

Abstract
Spinal cord stimulation (SCS) is an effective modality for pain treatment, yet its underlying mechanisms remain elusive. Neurokinin 1 receptor–positive (NK1R+) neurons in spinal lamina I play a pivotal role in pain transmission. To enhance our mechanistic understanding of SCS-induced analgesia, we investigated how different SCS paradigms modulate the activation of NK1R+ neurons, by developing NK1R-Cre;GCaMP6s transgenic mice and using in vivo calcium imaging of superficial NK1R+ neurons under anesthesia (1.5% isoflurane). Neurokinin 1 receptor–positive neurons in the lumbar spinal cord (L4-5) showed a greater activation by electrical test stimulation (TS, 3.0 mA, 1 Hz) at the hindpaw at 2 weeks after tibia-sparing nerve injury (SNI-t) than in naïve mice. Spinal cord stimulation was then delivered through a bipolar plate electrode placed epidurally at L1-2 level. The short-term 50-Hz high-intensity SCS (80% motor threshold [MoT], 10 minutes) induced robust and prolonged inhibition of NK1R+ neuronal responses to TS in both naïve and SNI-t mice. The 30-minute 50-Hz and 900-Hz SCS applied at moderate intensity (50% MoT) also significantly inhibited neuronal responses in SNI-t mice. However, at low intensity (20% MoT), the 30-minute 900-Hz SCS only induced persistent neuronal inhibition in naïve mice, but not in SNI-t mice. In conclusion, both 10-minute high-intensity SCS and 30-minute SCS at moderate intensity inhibit the activation of superficial NK1R+ neurons, potentially attenuating spinal nociceptive transmission. Furthermore, in vivo calcium imaging of NK1R+ neurons provides a new approach for exploring the spinal neuronal mechanisms of pain inhibition by neuromodulation pain therapies.
The clinical effect of dienogest on urinary and sexual symptoms in endometriosis patients
Authors: Long Cheng-Yu , Chang Chih-Ting , Lin Kun-Ling , Yeh Chang-Lin , Feng Chien-Wei , Loo Zi-Xi 
Published: August 2024

Background:
To evaluate the effect of dienogest on urinary symptoms and sexual functioning within a 6-month follow-up period.

Methods:
We recruited 22 women with symptoms with dysmenorrhea, deep dyspareunia, and dyschezia accompanied with irritative urinary symptoms including frequency and urgency at Kaohsiung Medical University Chung-Ho Memorial Hospital from 2017 Jan 1 to 2019 Jan 1. The diagnosis of endometriosis mainly focused on vaginal examination and transvaginal ultrasound was performed in each patient. The participating patients took a daily dose of 2 mg Dienogest and underwent outpatient visits at the beginning, 1, 2, 3, and 6 months following treatment.

Results:
Our data showed a significant improvement in the visual Analog Scale (VAS) score from the first month till the sixth month after DNG treatment. The Overactive Bladder Symptom Score (OABSS), Urogenital Distress Inventory (UDI-6), and Incontinence Impact Questionnaire (IIQ-7) were significantly improved after the DNG treatment. Besides, serum estradiol was also decreased. Our data also showed that DNG treatment for 6 months did not affect Female Sexual Function Index (FSFI) score. Some patients with heavy menstruation also improved; however, some patients with regular periods missed or skipped a period after DNG treatment, while other adverse effects were also observed.

Conclusion:
Our study demonstrated that DNG could not only alleviate endometriosis pelvic pain but reduce urinary symptoms within the 6-month follow-up as well. DNG did not affect sexual function as measured by the FSFI score, although some adverse effects were recorded.
The preferred surgical choice for intermediate-risk papillary thyroid cancer: total thyroidectomy or lobectomy? A systematic review and meta-analysis
Authors: Cao Mingyu , Yu Tiexin , Miao Xingyu , Wu Zhijing , Wang Wenlong 
Published: August 2024

Background:
The optimal surgical approach for intermediate-risk papillary thyroid carcinoma (IR-PTC) (according to ATA definition), whether total thyroidectomy (TT) or lobectomy (LT), has remained a contentious clinical gray area for several decades. This systematic review and meta-analysis aim to provide robust evidence and address this clinical dilemma comprehensively.

Materials and methods:
A comprehensive literature search was conducted in Pubmed, Embase, Web of Science, and the Cochrane Library from 1st January 2009 to 29th December 2023 to evaluate the impact of different surgical options (TT or LT) on patients with IR-PTC. The primary outcomes included survival, recurrence rates, and postoperative complications. I
2 and sensitivity analysis was used to explore the heterogeneity.

Results:
A total of 8 studies involving 2984 participants were included in this meta-analysis and systematic review. The results indicated that LT was a superior choice for mitigating complications compared to TT [risk ratio (RR), 0.32; 95% CI: 0.24–0.44, P<0.01], particularly for transient complications (RR, 0.24; 95% CI: 0.08–0.65, P<0.01), such as the transient parathyroid dysfunction (RR, 0.04; 95% CI: 0.01–0.15, P<0.01). However, TT did not increase the risk of recurrent laryngeal nerve palsy (RR, 0.78; 95% CI: 0.24–2.47, P=0.67), hemorrhage/seroma (RR, 0.77; 95% CI: 0.48–1.25, P=0.30), and permanent complications (RR, 0.18; 95% CI: 0.02–1.42, P=0.10). Besides, both LT and TT presented similar effect on survival outcomes (overall survival: RR, 1.00; 95% CI: 0.97–1.03, P=0.92, disease-specific survival: RR, 0.99; 95% CI: 0.97–1.02, P=0.69, recurrence-free survival: RR, 1.00; 95% CI: 0.96–1.05, P=0.86), recurrence (RR, 1.05; 95% CI: 0.76–1.46, P=0.76).

Conclusion:
The present meta-analysis revealed that TT did not yield improved outcomes in IR-PTC patients, but was associated with an increased incidence of temporary complications. In light of these findings, it may be advisable to consider LT as the optimal choice for IR-PTC patients.
Report of a novel recurrent homozygous variant c.620A>T in three unrelated families with thiamine metabolism dysfunction syndrome 5 and review of literature
Authors: Mascarenhas Selinda , Yeole Mayuri , Rao Lakshmi Priya , do Rosario Michelle C , Majethia Purvi , Nair Karthik Vijay , Sharma Suvasini , Barala Praveen Kumar , Puri Ratna Dua , Pal Swasti , Siddiqui Shahyan , Shukla Anju 
Published: August 2024

IntroductionBiallelic variants in thiamine pyrophosphokinase 1 (TPK1) are known to cause thiamine metabolism dysfunction syndrome 5 (THMD5). This disorder is characterized by neuroregression, ataxia and dystonia with basal ganglia abnormalities on neuroimaging. To date, 27 families have been reported with THMD5 due to variants inTPK1.MethodsWe ascertained three individuals from three unrelated families. Singleton exome sequencing was performed on all three individuals, followed byin silicomutagenesis of the mutant TPK protein. Additionally, we reviewed the genotypic and phenotypic information of 27 previously reported individuals with THMD5.ResultsSingleton exome sequencing revealed a novel homozygous variant c.620A>T p.(Asp207Val) inTPK1(NM_022445.4) in all three individuals.In silicomutagenesis of the mutant protein revealed a decrease in protein stability and altered interactions with its neighboring residues compared to the wild-type protein. Thus, based on strikingly similar clinical and radiological findings compared to the previously reported individuals and with the support ofin silicomutagenesis findings, the above-mentioned variant appears to be the probable cause for the condition observed in the affected individuals in this study.ConclusionWe report a novel homozygous variant inTPK1, which appears to be recurrent among the Indian population.
Dilated aorta in CNOT3-related neurodevelopmental disorder: ‘expanding’ the phenotype
Authors: Lau Sandra Hui Min , Jiin Ying Lim , Goh Chew Yin Jasmine , Choo Jonathan , Chow Cristelle , Ling Simon , Ng Yong Hong , Yi Hua Tan , Teo Jing Xian , Chua Khi Pin , Chin Minning , Lim Weng Khong , Jamuar Saumya Shekhar , Lai Angeline Hwei Meeng , Goh Jeannette Lay Kuan 
Published: August 2024

Introduction
Neurodevelopmental disorders (NDDs) comprise conditions that emerge during the child’s development and contribute significantly to global health and economic burdens. De novo variants in CNOT3 have been linked to NDDs and understanding the genotype–phenotype relationship between CNOT3 and NDDs will aid in improving diagnosis and management.

Methods
In this study, we report a case of a patient with CNOT3-related NDD who presented with progressive aortic dilatation, a feature not reported previously.

Results
Our patient presented with intellectual disorder, dysmorphic facial features, and cardiac anomalies, notably progressive aortic dilatation – a novel finding in CNOT3-related NDD. Genetic testing identified a de novo 6.3 kbp intragenic deletion in CNOT3, providing a possible genetic basis for her condition.

Conclusion
This study presents the first case of CNOT3-related NDD in Southeast Asia, expanding the phenotype to include progressive aortic dilatation and suggesting merit in cardiac surveillance of patients with CNOT3-related NDD. It also emphasizes the importance of genetic testing in diagnosing complex NDD cases as well as reanalysis of ‘negative’ cases using advanced sequencing technologies to uncover potential hidden genetic etiologies in undiagnosed NDDs.
Allogeneic Hematopoietic Cell Transplantation With Reduced Toxicity Conditioning for Pediatric B Lymphoid Malignancy
Authors: Naito Yuki , Osone Shinya , Mitsuno Kohei , Kanayama Takuyo , Mayumi Azusa , Imamura Toshihiko , Iehara Tomoko 
Published: August 2024

Background:
Conventional conditioning regimens for children with lymphoid malignancy undergoing allogeneic hematopoietic cell transplantation (HCT) are myeloablative and involve high-dose total body irradiation (TBI). Such regimens are associated with significant late complications.

Observations:
Here, we used a reduced-toxicity conditioning regimen comprising fludarabine, cytarabine, melphalan, and low-dose TBI (FLAMEL) to treat 5 patients with lymphoid malignancy before HCT. Four patients maintained complete remission (range, 18 to 63 mo), whereas the remaining patient who had positive minimal residual disease (MRD) before HCT relapsed.

Conclusions:
FLAMEL might be a suitable conditioning regimen for children with lymphoid malignancy if pre-HCT MRD is negative.
Late Relapse in Genetically Determined Infantile Myofibromatosis. A Case Report and Brief Focus on Recurrences
Authors: Conte Alessio , De Padova Damiana , Giglio Serena , Livellara Virginia , Manzitti Carla , De Marco Patrizia , Capra Valeria , Sorrentino Stefania 
Published: August 2024

Background:
Infantile myofibromatosis (IM) is a rare disorder characterized by benign tumors in the skin, subcutaneous tissue, muscle, and occasionally viscera. IM can be hereditary due to PDGFRB or NOTCH3 variants. Treatment is mainly conservative or surgical. Combination regimens have been used in case of disseminated disease.

Observation:
We present relapsed disease of IM 11 years after diagnosis in a 2-year-old child initially treated by microscopically complete resection. A new heterozygous c.1687G>A (p.Glu563Lys) mutation in the PDGFRB gene was identified (considered likely pathogenic).

Conclusions:
In association with initial treatment, genetic testing is crucial for tailored clinical practice and follow-up in patients diagnosed with IM.