bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictors of surgical complications in boys with hypospadias: data from an international registry
Authors: Scougall Kathryn , Bryce Jillian , Baronio Federico , Boal Rachel L , Castera Jose Roberto , Castro Sebastián , Cheetham Tim , Costa Eduardo Corrêa , Darendeliler Feyza , Davies Justin H , Dirlewanger Mirjam , Gazdagh Gabriella , Globa Evgenia , Guerra-Junior Gil , Guran Tulay , Herrmann Gloria , Holterhus Paul-Martin , Akgül Ahsen Karagözlü , Markosyan Renata , McElreavey Kenneth , Miranda Marcio Lopes , Nordenstrom Anna , O’Toole Stuart , Poyrazoglu Sukran , Russo Gianni , Schwitzgebel Valerie , Stancampiano Marianna , Steigert Michael , Ahmed S Faisal , Lucas-Herald Angela K
Published: October 2023

Background

Complications are frequently reported after hypospadias repair and there is a need to understand the factors that influence their occurrence.

Methods

Data from boys with hypospadias born between 2000 and 2020 were obtained from the International Disorders of Sex Development (I-DSD) Registry. Logistic regressions, fisher’s exact tests and spearman’s correlation tests were performed on the data to assess associations between clinical factors and complication rates.

Results

Of the 551 eligible boys, data were available on 160 (29%). Within the cohort, the median (range) External Masculinization Score (EMS) was 6 (2, 9). All presented with one or more additional genital malformation and 61 (38%) presented with additional extragenital malformations. Disorders of androgen action, androgen synthesis and gonadal development were diagnosed in 28 (18%), 22 (14%) and 9 (6%) boys, respectively. The remaining 101 (62%) patients were diagnosed as having non-specific 46,XY Disorders of Sex Development. Eighty (50%) boys had evidence of abnormal biochemistry, and gene variants were identified in 42 (26%). Median age at first hypospadias surgery was 2 years (0, 9), and median length of follow-up was 5 years (0, 17). Postsurgical complications were noted in 102 (64%) boys. There were no significant associations with postsurgical complications.

Conclusions

Boys with proximal hypospadias in the I-DSD Registry have high rates of additional comorbidities and a high risk of postoperative complications. No clinical factors were significantly associated with complication rates. High complication rates with no observable cause suggest the involvement of other factors which need investigation.
Spin 12 from gluons
Authors: Balachandran A. P.
Published: October 2023

The theta vacuum in QCD is obtained from the standard vacuum, after twisting by the exponential of the Chern–Simons term. However, a question remains–what is the quantum operator [Formula: see text] for winding number 1? We construct this operator [Formula: see text] in this note. The Poincaré rotation generators commute with it only if they are augmented by the spin [Formula: see text] representation of the Lorentz group, coming from large gauge transformations. This result is analogous to the well-known “spin-isopin” mixing result due to Jackiw and Rebbi [Phys. Rev. Lett. 36, 1116 (1976)], and Hasenfratz and ’t Hooft [Phys. Rev. Lett. 36, 1119 (1976)]. There is a similar result in fuzzy physics literature of Balachandran, Kurkcuoglu and Vaidya [Lectures on Fuzzy and Fuzzy Susy Physics (World Scientific Publishing Company, 2007)]. This shows that states can drastically affect representations of observables. This fact is further shown by charged states dressed by infrared clouds. Following Mund, Rehren and Schroer [arXiv:hep-th/2109.10342], we find that Lorentz invariance is spontaneously broken in these sectors. This result has been extended earlier to QCD (Balachandran, Nair, Pinzul, Reyes-Lega and Vaidya [arXiv:2112.08631 [hep-th]], reference given in the Final Remarks) where even the global QCD group is shown to be broken. It is argued that the escort fields of Mund, Rehren and Schroer [arXiv:hep-th/2109.10342] are the Higgs fields for Lorentz and color breaking. They are string-localized fields where the strings live in a union of de Sitter spaces. Their oscillations and those of the infrared cloud can generate the associated Goldstone modes.
Dark energy black holes with intermediate masses at high redshifts: An earlier generation of quasars and observations
Authors: Singh Anupam
Published: October 2023

Dark energy is the largest fraction of the energy density of our universe — yet it remains one of the enduring enigmas of our times. Here we show that dark energy can be used to solve 2 tantalizing mysteries of the observable universe. We build on existing models of dark energy linked to neutrino masses. In these models, dark energy can undergo phase transitions and form black holes. Here we look at the implications of the family structure of neutrinos for the phase transitions in dark energy and associated peaks in black hole formation. It has been previously shown that one of these peaks in black hole formation is associated with the observed peak in quasar formation at redshifts [Formula: see text]. Here, we predict that there will also be an earlier peak in the dark energy black holes at high redshifts [Formula: see text]. These dark energy black holes formed at high redshifts are Intermediate Mass Black Holes (IMBHs). These dark energy black holes at large redshift can help explain both the EDGES observations and the observations of large Supermassive Black Holes (SMBHs) at redshifts of 7 or larger. This work directs us to actively look for these dark energy black holes at these high redshifts as predicted here through targeted searches for these black holes at the redshifts [Formula: see text] near 18. There is a slight dependence of the location of the peak on the lightest neutrino mass. This may enable a measurement of the lightest neutrino mass — something which has eluded us so far. Finding these dark energy black holes of Intermediate Mass should be within the reach of upcoming observations — particularly with the James Webb Space Telescope — but perhaps also through the use of other innovative techniques focusing specifically on the redshifts [Formula: see text] around 18.
Automatic Design of Dynamic Collaboration Strategies for Machines and Automated Guided Vehicles via Multiobjective Genetic Programming
Authors: Xin Bin , Lu Sai , He Yingmei , Wang Qing , Deng Fang
Published: October 2023

In the flexible manufacturing system (FMS), the automated guided vehicles (AGVs) have been widely applied to the material logistics. The transporting phases of AGVs and the processing phases of machines are alternately executed and form the production flow. The two kinds of phases will both influence the completing time and cause energy consumption and are difficult to decouple. Therefore, in this paper, we focus on the dynamic collaboration problem between processing machines and AGVs (DCPMA) and establish a multiobjective optimization model to minimize the makespan and the energy consumption of FMS. In order to solve DCPMA, we propose a novel genetic programming (GP) to evolve collaboration strategies. In GP, 10 status statistics related to the handling time and energy consumption are selected into GP terminal set to express the GP tree. During dynamic simulation, each collaboration strategy evaluated by GP will dynamically select the job-machine-AGV scheme combination with the highest priority calculated from the GP tree. In addition, a series of generation operators and selection operators are customized for DCPMA. Finally, the training and testing results show that the proposed GP is superior to 28 combinations of basic collaboration strategies, and has better adaptability and scalability for various scenarios.
IDSSL: Intent Detection Module Based on Self-Supervised Learning for Trajectory Prediction
Authors: Jin Chenyan , Kuang Sipeng , Cui Peng , Zhang Ya
Published: October 2023

Trajectory prediction models play a crucial role in various applications such as autonomous driving and human–robot interaction. For trajectory prediction models, understanding and accounting for the intentions of vehicles, such as whether they intend to change lanes, make turns, or maintain their current course, is vital for enhancing the safety and efficiency of autonomous systems. However, one significant limitation of some existing trajectory prediction models is their failure to fully consider the impact of vehicle intentions on agent trajectories. This paper addresses the problem that some existing trajectory prediction models do not fully consider the impact of vehicle intentions on agent trajectories. To tackle this challenge, we propose a self-supervised learning-based module for detecting vehicle intentions, which can be added to most trajectory prediction models. The module consists of a simple and effective pretext task and a lightweight intent detection model. We conduct extensive experiments on a large-scale motion forecasting benchmark to demonstrate the effectiveness of the proposed approach in improving the performance of trajectory prediction baselines.
Stressed Speech Emotion Recognition Using Teager Energy and Spectral Feature Fusion with Feature Optimization
Authors: Bandela Surekha Reddy , Siva Priyanka S. , Sunil Kumar K. , Vijay Bhaskar Reddy Y. , Berhanu Afework Aemro
Published: October 2023

The objective of speech emotion recognition (SER) is to enhance man–machine interface. It can also be used to cover the physiological state of a person in critical situations. In recent time, speech emotion recognition also finds its operations in medicine and forensics. A new feature extraction technique using Teager energy operator (TEO) is proposed for the detection of stressed emotions as Teager energy‐autocorrelation envelope (TEO‐Auto‐Env). TEO is basically designed for increasing the energies of the stressed speech signals whose energies are reduced during the speech production process and hence used in this analysis. A stressed speech emotion recognition (SSER) system is developed using TEO‐Auto‐Env and spectral feature combination for detecting the emotions. The spectral features considered are Mel‐frequency cepstral coefficients (MFCC), linear prediction cepstral coefficients (LPCC), and relative spectra–perceptual linear prediction (RASTA‐PLP). EMO‐DB (German), EMOVO (Italian), IITKGP (Telugu), and EMA (English) databases are used in this analysis. The classification of the emotions is carried out using the k‐nearest neighborhood (k‐NN) classifier for gender‐dependent (GD) and speaker‐independent (SI) cases. The proposed SSER system provides improved accuracy compared to the existing ones. Average recall is used for performance evaluation. The highest classification accuracy is achieved using the feature combination of TEO‐Auto‐Env, MFCC, and LPCC features with 91.4% (SI), 91.4% (GD‐male), and 93.1%(GD‐female) for EMO‐DB; 68.5% (SI), 68.5% (GD‐male), and 74.6% (GD‐female) for EMOVO; 90.6%(SI), 91% (GD‐male), and 92.3% (GD‐female) for EMA; and 95.1% (GD‐female) for IITKGP female database.
Walk‐to‐Charge Technology: Exploring Efficient Energy Harvesting Solutions for Smart Electronics
Authors: Beniwal Ruby , Kalra Shruti , Beniwal Narendra Singh , Mazumdar Hirak , Singhal Ashish Kumar , Singh Sunil Kumar
Published: October 2023

Wearable sensors offer great potential in sports, fitness, and medicine. However, their limited battery life poses a major obstacle to their widespread use. This paper explores various energy solutions to extend the battery life of wearable sensors. The first part of the paper focuses on hardware improvements for wearable sensors, such as employing low‐power sensors, energy‐ efficient microcontrollers, and power management circuits. The second part discusses the utilization of solar, thermal, and kinetic energy harvesting techniques to power wearable sensors. These methods aim to harness energy from the environment to supplement or replace battery power. The third part examines wireless power transfer techniques like radio frequency and magnetic resonance, which enable continuous power supply to wearable sensors without the need for physical connections. Software optimization is also highlighted as a crucial aspect in reducing energy consumption. This involves developing efficient algorithms for data processing and transmission, as well as implementing sleep and wake‐up modes to minimize power usage during idle periods. Furthermore, the paper emphasizes the importance of user interaction and behavior in improving energy efficiency. It suggests the development of user‐friendly interfaces and providing users with feedback on their energy usage.
Synthesis, Characterization, and Biological Evaluation of Gabapentinoid Hybrids with Isoindole-1,3(2H)-Dione Moiety as Potential Antioxidant, Antimicrobial, and Anticancer Agents
Authors: Jabbour Mirna , Al-Khayat Mohammad Ammar , Al-Ktaifani Mahmoud
Published: October 2023

Purpose. To synthesize new isoindole-1,3(2H)-dione derivatives by molecular hybridization of gabapentin and pregabalin with phthalic anhydride derivatives and to evaluate their biological activity as promising antioxidant, antimicrobial, and anticancer agents. Method. Molecular hybridization was successfully achieved by two procedures; synthesized compounds were characterized using analytical and spectral methods. The free radical scavenging properties of synthesized compounds were evaluated using the DPPH method. The antibacterial activity of synthesized compounds and parent compounds was evaluated against two microbial Gram-positive and Gram-negative strains by the well diffusion method. Furthermore, we have studied the effect of compounds on proliferation, cell cycle, and cell death in two human cancer cell lines (Caco-2 and HCT-116). Results. Compounds 1, 3, and 4 exhibited a good free radical scavenging effect, and compound 3 is the most effective with IC50 value of 2.525 μmol/mL. All compounds showed antibacterial activity against Escherichia coli and Staphylococcus aureus related to concentration, while parent drugs did not exhibit any antibacterial effect. Compounds 1 and 2 showed a good zone of inhibition against E. coli at micromolar concentrations, and they are more effective than Gentamicin Sulfate. Treatment with the studied compounds suppresses proliferation, arrests progress throughout the cell cycle, and induces apoptosis in Caco-2 and HCT-116 cancer cells. Compound 2 is highly effective against Caco-2 cells and more effective than thalidomide, with IC50 value less than 1 μmol/L. Conclusion. Our results showed that molecular hybridization of gabapentin and pregabalin in the isoindole-1,3(2H)-dione moiety results in promising anticancer and antimicrobial molecules. Results of this preliminary study show that halogenation of the isoindole-1,3(2H)-dione moiety improves antimicrobial and anticancer activity and that tetra-brominated derivatives are comparable to or more effective than related tetra-chlorinated derivatives.
Artificial Neural Network‐Based Experimental Investigations for Sliding Mode Control of an Induction Motor in Power Steering Applications
Authors: Parimalasundar E. , Senthilkumar R. , Kumar B. Hemanth , Janardhan K. , Singh Arvind R. , Bajaj Mohit , Bereznychenko Viktoriia
Published: October 2023

Sliding mode control (SMC) of induction motor is a new concept in the current scenario, as it seeks to improve torque control accuracy and power steering efficiency through the use of pulse width modulation schemes. Furthermore, artificial neural network‐based sliding mode control is applied to a squirrel cage induction motor, which is used in the steering control of automobiles. The artificial neural network (ANN)‐based SMC is more popular due to its robustness and good stability in external parameter variation. Additionally, an SMC and an ANN‐based SMC are employed to compute the torque and flux, improving performance for power steering applications. The performance of the designed model is validated through MATLAB/Simulink and experimental models with different controllers under various operating conditions. The controller has been embedded into a TMS320F28335 controller, and performances have been evaluated. The performance analyses of induction motor using different controllers are performed. The transient performances of induction motor such as delay time, rise time, settling time, and steady‐state error are investigated. The proposed work is analysed by using a mathematical model and implemented in a test‐bench model for validation.
Tetramethylpyrazine Attenuates Radiation-Induced Ototoxicity in a Rat Model
Authors: Sahin Mustafa , Kaya Altan , Aytekin Aynur , Akay Ebru , Ozcan Ibrahim
Published: October 2023

Introduction: Tetramethylpyrazine (TMP) is a chemical compound, which has been shown to possess numerous biological features such as anticoagulation, inhibition of platelet aggregation, anti-inflammation, capillary dilatation, improvement in microcirculation, and protection against reactive oxygen radicals. The aim of the present study was to investigate the protective effect of TMP against radiation-induced ototoxicity. Materials and Methods: 40 rats were divided into four groups. The first group was irradiated for 5 days. The second group received a single dose of 140 mg/kg/day intraperitoneal TMP given to the rats 30 min before radiotherapy (RT) for 5 days. The third group received a single dose of 140 mg/kg/day i.p. TMP for 5 days, whereas the fourth group was administered saline. All rats underwent distortion product otoacoustic emission (DPOAE) and auditory brainstem response measurements before and after the application. The temporal bulla of animals was removed for immunohistopathological examination. Results: Signal-noise ratio values were significantly decreased in the RT group for the frequencies of 2–32 kHz after RT (p < 0.05), whereas the difference was not significant in terms of pre- and posttreatment values for the other groups. Also in the RT group, the ABR thresholds were significantly increased after treatment. In H&E staining, the mean scores for outer hair cells (OHCs), stria vascularis (SV), and spiral ganglion (SG) injuries were significantly higher in RT and RT + TMP groups than in the other groups. The mean OHCs and SV injury scores were also significantly higher in the RT group than in the RT + TMP group (p < 0.05). The number of cochleas that showed cytoplasmic caspase-3 immunoreactivity in the OHC, SV, and SG was significantly higher in RT and RT + TMP groups than in the other groups. Conclusion: The findings of the present study suggest that TMP may have a therapeutic potential for preventing sensorineural hearing loss (SNHL) related to RT.
Mutations in a High-Grade Micropapillary Urothelial Carcinoma of the Renal Pelvis: A Case Report
Authors: Uppaluri Kalyan Ram , Kambalachenu Himavanth Reddy , Challa Hima Jyothi , Raghuram Y Saadvik , Gadicherla Ramya , Ketavath Srinivas , Palasamudram Kalyani , Sri Manjari K.
Published: October 2023

Micropapillary urothelial carcinoma (MPUC) of the renal pelvis is an upper tract urothelial carcinoma originating in the renal pelvis region. Few genetic studies are available, and the mechanism of pathogenesis of genetically driven models is unclear. We report a case of genomic alterations in MPUC of the renal pelvis and compare the results with existing literature. DNA was extracted, followed by the next-generation sequencing of 351 oncogenes and tumor suppressor genes. Targeted gene sequencing analysis revealed somatic variants in ERBB2, KMT2C, FOXA1, and germline variants in CDKN1B, ELF3, TP53, and RB1 genes. The present case study sheds light on recognizing genetic variants in high-grade MPUC of the renal pelvis. Understanding molecular mechanisms helps with better prognostication and development of more effective therapeutics and treatment.
Miliary Tuberculosis during R-MPV Therapy in an Elderly Patient with Primary Central Nerve System Lymphoma: A Case Report
Authors: Take Yushiro , Shirahata Mitsuaki , Sakai Jun , Kubota Yuichi , Suzuki Tomonari , Adachi Jun-ichi , Maesaki Shigefumi , Mishima Kazuhiko , Nishikawa Ryo
Published: October 2023

Most elderly patients with tuberculosis (TB) have previously been infected with Mycobacterium tuberculosis, which remains dormant in the body for decades and may reactivate when their immunity declines due to underlying diseases. Elderly cancer patients are at a high risk for TB, and the treatment of TB reactivation in these patients is challenging. Among cancer patients, the incidence of TB reactivation is the highest in lymphoma patients. However, the impact of chemotherapy on TB reactivation in lymphoma patients is unknown. We report the case of an immunocompetent elderly patient with primary central nervous system lymphoma (PCNSL) having no prior history of TB, who developed miliary TB during multiagent chemotherapy consisting of rituximab, high-dose methotrexate, procarbazine, and vincristine (R-MPV therapy). Retrospectively, the chest computed tomography showed calcification of the pleura, suggesting that the patient had a latent tuberculosis infection (LTBI) and developed miliary TB from the reactivation of TB triggered by the R-MPV therapy. Our case emphasizes that when chemotherapy is administered to patients with PCNSL, interferon-gamma release assay (IGRA) should be performed if there are findings on chest examination suggestive of LTBI, such as pleural calcification, and if IGRA is positive, chemotherapy should be given concurrently with LTBI treatment.
“Nicht so anstrengend wie erwartet”: Wie ein Fokus auf Erwartungsverletzungen die Wirksamkeit von Verhaltensaktivierung bei Depressionen steigern kann
Authors: Kube Tobias , Jakobs Sophia
Published: October 2023

Verhaltensaktivierung ist ein zentraler Bestandteil der kognitiven Verhaltenstherapie bei depressiven Störungen. Befunde aus der Grundlagenforschung zum inhibitorischen Lernen und deren klinische Anwendungen legen nahe, dass die Wirksamkeit von Verhaltensaktivierung zusätzlich gesteigert werden könnte, wenn bei der Durchführung ein besonderer Fokus auf das Erleben von Erwartungsverletzungen gelegt wird. So wird in diesem Artikel ein Behandlungsansatz vorgestellt, der die Verhaltensaktivierung um den Aspekt der Erwartungsverletzung ergänzt. Zentral ist dabei die Erfahrung, dass das Durchführen von geplanten Aktivitäten für Depressionspatient:innen meist weniger anstrengend als erwartet ist und mehr Freude als erwartet macht. In der Nachbesprechung wird zudem die nachhaltige Verarbeitung einer solchen erwartungsverletzenden Erfahrung besonders gefördert, indem einer nachträglichen Entwertung der Erfahrung durch die Patient:innen entgegengewirkt wird. So lernen die Patient:innen, dass sie aufgrund der Depression dazu neigen, Aktivitäten als unverhältnismäßig aversiv anzunehmen, sich diese Erwartung jedoch in aller Regel nicht bestätigt. Dadurch trauen sie sich in der Folge mehr zu und können zukünftige Aktivitäten optimistischer angehen. In einer kleinen Machbarkeitsstudie bei teilstationär behandelten Depressionspatient:innen (N = 7) zeigte sich, dass der hier vorgestellte Behandlungsansatz gut umsetzbar ist und von den Patient:innen gut angenommen wird. Dies kann die Grundlage für eine größer angelegte klinische Studie zur Wirksamkeitsprüfung sein und eine Weiterentwicklung der Verhaltensaktivierung anstoßen.
Hybrid Method for Peritoneal Dialysis Catheter Insertion: A New Technique for Improved Outcomes and Reduced Costs
Authors: Li Szu-Yuan , Chen Cheng-Yen , Tsai Ming-Tsun , Lin Niang-Cheng , Liu Chin-Su , Lin Chih-Ching
Published: October 2023

Introduction: Peritoneal dialysis (PD) is a well-established treatment choice for end-stage kidney disease (ESKD). While there are several methods for PD catheter insertion, they each have limitations. In this study, we present a new hybrid method for PD catheter insertion and compare it to the conventional laparoscopic method. Methods: This retrospective study included 171 patients who were undergoing their first PD catheter insertion, and a total of 20% of the enrolled patients had a past medical history of abdominal surgery. Out of these, 101 patients underwent the laparoscopic method and 70 underwent a new invented hybrid method. The study aimed to compare the surgical outcomes, incidence of early and late complications, hospital stay, and medical expenses between the two groups. Results: There were no notable differences in basic demographic features and comorbid conditions between the two groups. The results of our data revealed that the hybrid group had a significantly shorter break-in period and did not require temporary hemodialysis. Additionally, length of hospital stay and medical costs were significantly lower in the hybrid group (all p < 0.05). The incidence of early complications was lower in the hybrid group, while the incidence of late complications was comparable between the two groups. Conclusion: Our study demonstrates that the hybrid method of PD catheter insertion provides a safe and efficient alternative to the traditional laparoscopic method, enabling urgent-start PD and reducing hospital stays and medical expenses. Our findings support the use of the hybrid method as a new standard of care for ESKD patients undergoing PD catheter insertion.
Cilostazol versus Aspirin or Clopidogrel for Reducing Post-Stroke Aspiration Pneumonia: A Nationwide Retrospective Cohort Study
Authors: Sato So , Yamana Hayato , Kumazawa Ryosuke , Watanabe Hideaki , Fujita Asahi , Matsui Hiroki , Fushimi Kiyohide , Yasunaga Hideo
Published: October 2023

Introduction: The association between the use of cilostazol as a post-stroke antiplatelet medication and a reduction in post-stroke pneumonia has been suggested. However, whether cilostazol has a greater preventive effect against post-stroke aspiration pneumonia (AP) than other antiplatelet medications remains unclear. Thus, this study aimed to evaluate whether cilostazol has a greater preventive effect against post-stroke AP than aspirin or clopidogrel. Methods: Through the Japanese Diagnosis Procedure Combination database, we identified patients who were hospitalized for ischemic stroke between April 2012 and September 2019. We performed 1:1 propensity score matching between patients who received cilostazol alone at discharge and those who received aspirin or clopidogrel alone at discharge. The primary outcome was the 90-day readmission for post-stroke AP. The occurrence of recurrent ischemic stroke within 90 days was also evaluated. Results: Among the 305,543 eligible patients with ischemic stroke, 65,141 (21%), 104,157 (34%), and 136,245 (45%) received cilostazol, aspirin, and clopidogrel, respectively. Propensity score matching generated 65,125 pairs. The cilostazol group had a higher proportion of 90-day post-stroke readmissions with AP than the aspirin or clopidogrel groups (1.5% vs. 1.2%, p < 0.001). The proportion of patients with recurrent ischemic stroke within 90 days was also higher in the cilostazol group (2.4% vs. 2.2%, p = 0.017). Conclusion: The present study suggests that cilostazol may not have a greater effect on preventing post-stroke AP within 90 days than other antiplatelet medications. Nevertheless, further randomized controlled trials with longer follow-up periods are warranted.
Mefloquine-Induced Inner Ear Damage and Preventive Effects of Electrical Stimulation: An Electrophysiological Study
Authors: Ali-Nazari Mohammad Mahdi , Rahbar Nariman , Haddadzade Niri Hassan , Vasaghi-Gharamaleki Behnoosh
Published: October 2023

Introduction: Mefloquine is an antimalarial medicine used to prevent and treat malaria. This medicine has some side effects, including ototoxicity. This study, which was designed in two phases, aimed to investigate the side effects of mefloquine and evaluate the preventive effects of electrical stimulation on these side effects. Methods: In the first phase, two doses of mefloquine (50 and 200 μM) were injected into male rats, and after 7 days, they were evaluated by an auditory brainstem response (ABR) test. In the second phase, electrical stimulation was applied for 10 days, and then a toxic dose of mefloquine was injected. Similar to the first phase of the study, the animals were evaluated by an ABR test after 7 days. Results: In the first phase, the results showed that a high dose of mefloquine increased the ABR threshold and wave I latency; however, these changes were not observed in the second phase. Conclusion: Application of electrical stimulation could prevent the ototoxic effects of mefloquine. According to the findings of the present study, electrical stimulation can be used as a preconditioner to prevent the ototoxic effects of mefloquine.
Endometrial Cancer Diagnosed at an Early Stage during Lynch Syndrome Surveillance: A Case Report
Authors: Umemiya Maki , Horikawa Naoki , Kanai Ami , Saeki Ayaka , Ida Kohei , Makio Satoru , Yoshida Teruki , Tsuji Mitsuru , Gou Rei , Tani Hirohiko , Usui Takeshi , Kosaka Kenzo
Published: October 2023

Lynch syndrome is an autosomal dominant inherited disorder caused by a germline pathogenic variant in DNA mismatch repair genes, resulting in multi-organ cancer. Annual transvaginal ultrasonography and endometrial biopsy are recommended for endometrial cancer surveillance in patients with Lynch syndrome in several guidelines; however, evidence is limited. Here, we present the case of a 51-year-old woman with endometrial cancer who underwent robot-assisted laparoscopic simple hysterectomy at an early stage detected by Lynch syndrome surveillance. The patient was a 51-year-old gravida zero woman without any medical history or symptoms. Her sister suffered from bladder, breast, rectal, and endometrial cancer and was diagnosed with Lynch syndrome using a hereditary cancer panel test (VistaSeq®). During gynecologic surveillance, the patient’s endometrial cytology was classified as Papanicolaou class III. Therefore, she underwent endometrial curettage with hysteroscopy and was diagnosed with atypical endometrial hyperplasia. Robot-assisted hysterectomy was performed with a final pathological diagnosis of endometrial cancer (endometrioid carcinoma, Grade 1), stage 1A. She has remained disease-free for more than 12 months. Owing to advances in genetic medicine, prophylactic and therapeutic surgeries for hereditary cancers are increasing. To achieve an early diagnosis and treatment of Lynch syndrome-associated cancers, the importance of Lynch syndrome surveillance should be more widely recognized.
Effective Management of Nasal Vestibule Squamous Cell Carcinoma with Cemiplimab: A Case Report
Authors: Costabile Ferdinando , Donnarumma Marianna , Piscosquito Arianna , Ingenito Concetta , Iuliucci Michela Rosaria , Buonerba Carlo , Di Lorenzo Giuseppe , Di Trolio Rossella
Published: October 2023

Nasal vestibule squamous cell carcinoma (SCC) is a rare malignancy with limited treatment options. This case report presents an 83-year-old female with SCC of the nasal vestibule who was ineligible for surgery or radiotherapy due to various factors. The patient was successfully treated with cemiplimab, a systemic anti-PD-1 antibody, resulting in a remarkable tumor reduction without any observed side effects. This is the first reported case of nasal vestibule SCC treated with cemiplimab, highlighting its potential as a promising therapeutic option.
Prognostic Ability of Nutritional Indices for Outcomes of Bladder Cancer: A Systematic Review and Meta-Analysis
Authors: Jiao Huijie , Wang Lin , Zhou Xiaomei , Wu Jiacheng , Li Tiantian
Published: October 2023

Background: Nutrition has become an important parameter influencing the prognosis of several cancers. However, its impact on outcomes for bladder cancer (BC) is still unclear. This review examines the association between three commonly used nutritional indices, namely, the prognostic nutritional index (PNI), controlling nutritional status (CONUT), and the geriatric nutritional risk index (GNRI) and outcomes of BC. Methods: PubMed, CENTRAL, Scopus, Web of Science, Embase, and Google Scholar were explored for studies published up to April 13, 2023. Data from studies were pooled to examine the association between PNI, CONUT, or GNRI and overall survival (OS) and recurrence-free survival (RFS). Results: Thirteen studies were included. Meta-analysis demonstrated significantly poor OS with low PNI versus high PNI in BC patients (hazard ratio [HR]: 1.71; 95% confidence interval [CI]: 1.37, 2.14; I2 = 0%). This result remained significant in various subgroup analyses. However, no association was noted between PNI and RFS (HR: 1.22; 95% CI: 0.67, 2.24; I2 = 84%). Meta-analysis showed that patients with high CONUT scores had significantly poor OS (HR: 2.43; 95% CI: 1.82, 3.25; I2 = 0%) as well as RFS (HR: 2.90; 95% CI: 2.10, 4.01; I2 = 0%). Data on GNRI were scarce and conflicting. Conclusion: Limited data show that PNI and CONUT are predictive of outcomes in BC. Low PNI was associated with poor OS, while high CONUT was associated with poor OS and RFS. Data on GNRI are too scarce to obtain conclusions. Further studies are needed to supplement the results.
Low-Dose Oral Minoxidil for Alopecia: A Comprehensive Review
Authors: Gupta Aditya K. , Talukder Mesbah , Shemar Avner , Piraccini Bianca Maria , Tosti Antonella
Published: October 2023

Low-dose oral minoxidil (LDOM) has demonstrated a promising safety and efficacy profile in the treatment of various hair disorders, including male androgenetic alopecia (AGA) and female-pattern hair loss (FPHL); however, it lacks FDA approval. The usual LDOM starting dose for male AGA is 1–5 mg/day, depending on physician preference and the patient’s condition. For FPHL, it is 0.5–1 mg/day. The maximum dose is generally 5 mg/day. If patients respond well without major side effects, the dose may be gradually increased since the LDOM’s efficacy appears to be dose-dependent. Patients may use LDOM long term if the treatment outcome is satisfactory. The common side effects of LDOM are hypertrichosis and cardiovascular symptoms. Females are more prone to hypertrichosis than males. The side effects of LDOM can be categorized as (a) dose-dependent type A side effects (hypertrichosis and cardiovascular symptoms) and (b) idiosyncratic type B side effects (pericardial effusion). Minoxidil acts via multiple pathways. Although minoxidil has a relatively short half-life of around 4 h, its hypotensive effect may last approximately 72 h. Effective treatments for alopecia are limited. Therefore, LDOM could be an important addition to the available therapies for managing some hair disorders, including AGA.
A Novel Mutation of UMOD in a Chinese Family with IgA Nephropathy: A Case Report
Authors: Li Furong , Zou Huan , Liu Li , Xiao Tangli , Zhang Bo , Zhang Jun
Published: October 2023

IgA nephropathy (IgAN) is the most prevalent primary glomerulonephritis worldwide, with varying clinical presentations. The hereditary susceptibility to IgAN is rather complex. In this report, a Chinese case of IgAN was recruited. Renal biopsy showed the tubular atrophy and dilatation, but the glomerular lesions were rather weak except slight mesangial hyperplasia. Immunological staining of kidney tissue revealed the positive immunological staining of IgA and C3. By using whole-exome sequencing, a heterozygous variant in UMOD gene was found and was confirmed by Sanger sequencing. The variant in UMOD gene might contribute to the disease and this case helps understand the correlation of genotype and phenotypes of UMOD mutations.
A Case of Tumor Lysis Syndrome during Palliative Radiotherapy for Breast Cancer Metastases
Authors: Furusawa Mitsuhiro , Matsuishi Kozue , Horino Kei , Inoue Hideki , Abe Michio , Oya Natsuo
Published: October 2023

Tumor lysis syndrome (TLS) is the rapid disintegration of a malignant tumor treated with anticancer drugs or radiation, causing electrolyte abnormalities such as elevated uric acid levels, elevated potassium and phosphorus levels, and decreased calcium levels. These abnormalities can lead to hypotension, renal dysfunction, consciousness disorders, and even death in some cases. The current patient was a 65-year-old woman who had breast cancer with local invasion, lung metastasis, and bone metastasis from the time of the initial disease onset. Despite the administration of various chemotherapy and hormone therapy regimens, the tumor increased gradually, and at 2 years and 5 months after the initial onset, pain and bleeding from metastatic infiltration of the cervical lymph nodes were noted. Therefore, radiotherapy was indicated for palliation of pain and bleeding caused by metastatic invasion of the cervical lymph nodes. Irradiation (30 Gy/10fr) was planned with a 3-field technique using 4MVX and 10MVX. Approximately 11 h after the initial irradiation, symptoms such as respiratory distress, tachycardia, and hypotension were observed. Blood tests revealed hyperuricemia and hyperkalemia, leading to a diagnosis of TLS. Dialysis and electrolyte correction were immediately initiated resulting in normalization of electrolytes and stabilization of the blood pressure. It is crucial to understand that TLS is relatively rare but can occur after radiation therapy or in solid tumors, and warrants a prompt response if suspected based on symptoms or blood findings.
A Family with EEC Syndrome in the Son and ADULT Syndrome in His Father Caused by the c.797G>A (p.Arg266Gln) Pathogenic Variant in the TP63 Gene
Authors: Corona-Rivera Jorge Román , Rios-Flores Izabel Maryalexandra , Zenteno Juan Carlos , Peña-Padilla Christian , Castillo-Reyes Katia , Bobadilla-Morales Lucina , Corona-Rivera Alfredo , Acosta-Fernández Elizabeth , Bruckman-Jiménez Alejandro
Published: October 2023

Introduction: To our knowledge, there are few examples of intrafamilial variability involving two different TP63-linked morphopathies within a same family. Here, we describe a Mexican family in which the son had ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3 (EEC3), and his father acro-dermato-ungual-lacrimal-tooth (ADULT) syndrome, both heterozygous for the p.Arg266Gln pathogenic variant in TP63. Additionally, we reviewed the clinical information reported for this TP63 genotype. Case Presentation: The son of this family presented ectodermal defects (thin and sparse hair, mild nail dysplasia), tetramelic ectrodactyly, syndactyly, and nasolacrimal duct obstruction (NLDO), indicative of an EEC3 diagnosis. His father, however, exhibited severe NLDO, facial freckling, dental abnormalities, mild nail dysplasia, and a history of micturition problems, compatible with ADULT syndrome. Both were heterozygous for the NM_003722.5(TP63):c.797G>A (p.Arg266Gln) pathogenic variant in TP63. Discussion: This report expands the spectrum of intrafamilial variability confirming that this can include the expression of distinct types of TP63-related disorders among different members of the same family, whose implications should be also considered in genetic counseling. From our review, we observed that p.Arg266Gln variant seems to correlate particularly with the presence of NLDO, sparse hair/eyebrows, ridged/dystrophic nails, anodontia/hypodontia, and micturition difficulties, as well as for a minor frequency of cleft lip/cleft palate.
Methemoglobinemia in Hemodialysis Patients due to Acute Chlorine Intoxication: A Case Series Calling Attention on an Old Problem
Authors: Chávez-Iñiguez Jonathan S. , Medina-González Ramón , Ron-Magaña Ana , Madero Magdalena , Ramírez-Ramírez Amanda C. , Rifkin Brian S. , Torres-Vázquez Eduardo , Chávez-Alonso Gael , Gómez-Fregoso Juan A. , Rodríguez-García Gonzalo , Oseguera-González Alexa N. , Carmona-Morales Edgar J. , Murguia-Soto Cesar , Renoirte-López Karina , García-García Guillermo
Published: October 2023

Introduction: Hemodialysis uses municipal water that must be strictly purified and sterilized to be used for that procedure. Large amounts of decontaminants are often used, such as chlorine, and if these compounds are not subsequently removed they can be transferred to the blood of patients causing complications including methemoglobinemia. Methods: In this case series study, dialysis patients in one unit were evaluated. We reviewed clinical characteristics and laboratory findings obtained on the day when the water supply was disinfected with chlorine, with the aim to quantify methemoglobin concentrations. Our objective was to characterize the clinical presentation and management of patients who presented with methemoglobinemia on a specific index day. We also reviewed reported cases in the literature regarding this underreported complication. Results: Eight patients who presented with chlorine intoxication were evaluated. The methemoglobin concentrations were between 1.3% and 7.9% (reference value 0–1%). We believe this to be caused by water containing 0.78 mg/L of total chlorine. Seven patients presented with cyanosis, 4 with dizziness, 6 with dark brown blood, 4 with dyspnea, and 4 with headache and hemolytic anemia. Subjects were treated with supplemental oxygen, methylene blue, intravenous vitamin C, blood transfusions, and increased doses of erythropoietin. No patient died, and all continued with their usual hemodialysis sessions. Conclusion: Acute chlorine intoxication transferred by the water used during hemodialysis sessions can present with methemoglobinemia accompanied by cyanosis, oxygen desaturation, and hemolytic anemia. Chlorine levels should be carefully monitored in the water used for hemodialysis treatment.
Rapid Malignant Transformation of Tubulovillous Adenoma, Initially Presenting as McKittrick-Wheelock Syndrome: A Case Report
Authors: Purwanto Ibnu , Leo Benedreky , Purwanto Utomo Bambang , Sofii Imam , Dwianingsih Ery Kus , Ratnasari Neneng
Published: October 2023

Most cases of colorectal cancer develop from adenomatous polyps, slowly progressing within an average period of 8–10 years. McKittrick-Wheelock syndrome (MKWS) is a rare manifestation of tubulovillous adenoma. It generally presents as hypersecretory diarrhea with severe electrolyte and fluid depletion. Roughly, 5% of the published cases have reported malignant histopathology associated with MKWS, with little to no data regarding the malignant transformation process of those patients. Our patient was a 53-year-old Asian woman suffering from chronic secretory diarrhea, resulting in severe volume, electrolyte depletion, and prerenal azotemia, consistent for MKWS. Her symptoms initially improved with sulfasalazine but eventually worsened. She demonstrated signs of systemic (elevated leukocyte, CRP, and LDH) and local inflammation (dense lymphocyte infiltration in colorectal tissue) throughout the course of her disease. Serial pathological results showed rapid neoplastic progression of adenomatous polyp to adenocarcinoma within 1 year period. Surgical resection resulted in complete symptom resolution. Molecular examination showed a favorable profile of exon 4 Kirsten rat sarcoma viral oncogene homolog mutation, normal NRAS, BRAF, CDX2, and CK20 expressions. Her molecular pattern did not reflect the profile of an aggressive disease, suggesting the possibility of oncogenic processes outside the major pathways of adenoma to carcinoma progression. Chronic inflammation is a well-established risk factor for colorectal cancer, and prostaglandin E2 (PGE2) has been observed as one of the key regulators of tumor initiation and growth. PGE2 is also responsible for hypersecretory diarrhea associated with MKWS.
Remitting Seronegative Symmetrical Synovitis with Pitting Edema: A Case Report of an Immune-Related Adverse Event following Surgery
Authors: Janse van Rensburg Helena J. , Spiliopoulou Pavlina , Makhzoum Anas , Healy Brian D.
Published: October 2023

Immune checkpoint inhibitors (ICIs) have emerged as a novel class of anti-neoplastic agent in oncology. Their integration into practice has been accompanied by “immune-related adverse events” (irAEs) wherein off-target immune responses damage healthy tissues. Severe irAEs can cause irreversible organ dysfunction and death. Despite this, little is known about factors which predispose certain patients to develop irAEs or which precipitate their onset. Here, we report a case of a patient with melanoma who completed adjuvant immunotherapy, underwent elective hip replacement, and developed a rare rheumatologic irAE (remitting seronegative symmetrical synovitis with pitting edema) post-operatively. Mechanistically, we hypothesize that surgery contributed to irAE pathogenesis as a sensitizing event in which self-antigens were presented to an immune system with diminished peripheral tolerance in the context of recent ICI administration. This case highlights a need for future correlative analyses, investigating whether iatrogenic interventions such as surgery might be associated with irAE development.
A Case of Lamina Lucida-Type Linear IgA Disease Complicated by Colon Polyposis and Rectal Adenocarcinoma
Authors: Miyazaki Akiko , Itoi-Ochi Saori , Hayashi Mami , Ota Asako , Nagai Kengo , Inoue Shinya , Tomita Naohiro , Eguchi Hidetaka , Okazaki Yasushi , Ishida Hideyuki , Hashimoto Takashi
Published: October 2023

Linear IgA disease (LAD) is a rare autoimmune bullous disease characterized by IgA deposition in the basement membrane zone (BMZ). A 66-year-old male was treated for myelodysplastic syndrome at our hospital for 5 years, during which his condition remained stable. He visited our department because of erythema with itching, which appeared 1 year ago and gradually exacerbated with the development of blisters and erosions. During the first visit, multiple erythemas with erosions and crusts on their periphery were observed on the trunk and lower limbs. Histopathological examination revealed subepidermal blisters with inflammatory cell infiltration, mainly constituting of neutrophils, eosinophils, and lymphocytes. Direct and indirect immunofluorescence showed linear IgA deposits in the BMZ and IgA anti-BMZ antibodies, respectively, while immunoblotting using a concentrated culture supernatant of HaCaT cells detected IgA antibodies reactive to 120-kDa LAD-1. Accordingly, the patient was diagnosed with lamina lucida-type LAD. Subsequent colonoscopy revealed multiple colorectal polyps and rectal adenocarcinoma (Tis, N0, and M0). Multigene panel test showed an ATM variant of unknown significance but did not detect any pathogenic variants associated with intestinal polyposis syndrome. The skin lesions quickly resolved with oral diaphenylsulfone 50 mg/day and resection of the colorectal polyps and adenocarcinoma. To our knowledge, this is the first reported case of LAD associated with multiple colorectal polyps and rectal adenocarcinoma. Additionally, we also analyzed reported cases of LAD associated with malignancy from the literature.
Primary Hepatic Neuroendocrine Carcinoma with Metastasis to the Mesentery: A Case Report
Authors: Fernández-Ferreira Ricardo , Romero-López Ulises , Robles-Aviña Jorge Alberto , Rivas-Mendoza Uriel Norberto , González-Camacho Casandra , Valero-Gómez Alfredo , Barquet-Mata Omar Armando , Reyes-Gabiño Almira , Tovar-Figueroa Karen Analí , Ramírez-Villagrán Viridiana
Published: October 2023

Primary hepatic neuroendocrine carcinomas (PHNECs) are extremely rare, with only about 90 cases having been reported in the English-language literature. Among all neuroendocrine neoplasms, primary hepatic neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs) are extremely rare, accounting for 0.3% of NETs and 0.28–0.46% of malignant liver tumors. Additionally, primary hepatic NECs occur infrequently. The clinical diagnosis of primary hepatic NEC remains challenging because of its rarity and the lack of information about its characteristic appearance on images. Consequently, pathological examination through the performance of a preoperative liver tumor biopsy is essential for diagnosis. Due to the lack of availability of substantial high-quality data, there is no standard therapy for primary hepatic NEC. We present the first case of PHNEC metastasized to the mesentery reported in the English-language literature.