bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnosis and Treatment Challenges of Candida guilliermondii in Immunocompromised Patients: A Case Study in a Neutropenic AML Patient
Authors: Modi Dhruvi , Dessureault Sophie , Greene John
Published: July 2024

Although fungal infections causing intestinal perforation and necrosis are rare, they can be particularly dangerous in immunosuppressed patients, often leading to increased mortality rates and poor prognoses. Candida species are typically surface fungi, but in patients with compromised immune systems, they can invade the small intestine and cause angioinvasive infections. A case study involving a 30‐year‐old female with acute myeloid leukemia (AML) illustrates this phenomenon. The patient was presented with symptoms of abdominal pain, fever, diarrhea, recurrent episodes of intestinal necrosis, hematomas due to thrombocytopenia, and subsequent postoperative enterocutaneous fistulas. Extensive testing ruled out other possible causes of intestinal necrosis and enteritis, including Crohn’s and CMV diseases. Candida guilliermondi was ultimately identified in blood cultures from the periphery, peritoneal fluid, and intestinal biopsy of respected sections, indicating that it was responsible for intestinal invasion and necrosis. The patient was then treated with amphotericin B, cefepime, and metronidazole. This case highlights the potential severity of fungal infections in immunosuppressed patients, particularly Candida species, and the importance of prompt diagnosis and appropriate treatment.
Supplementary Video S1 from CRAVAT 4: Cancer-Related Analysis of Variants Toolkit
Authors: Masica David L. , Douville Christopher , Tokheim Collin , Bhattacharya Rohit , Kim RyangGuk , Moad Kyle , Ryan Michael C. , Karchin Rachel
Published: July 2024

Brief video tutorial for the mutation analysis package CRAVAT.
Supplementary Tables S1-S19 from Obesogenic High-Fat Diet and MYC Cooperate to Promote Lactate Accumulation and Tumor Microenvironment Remodeling in Prostate Cancer
Authors: Boufaied Nadia , Chetta Paolo , Hallal Tarek , Cacciatore Stefano , Lalli Daniela , Luthold Carole , Homsy Kevin , Imada Eddie L. , Syamala Sudeepa , Photopoulos Cornelia , Di Matteo Anna , de Polo Anna , Storaci Alessandra Maria , Huang Ying , Giunchi Francesca , Sheridan Patricia A. , Michelotti Gregory , Nguyen Quang-De , Zhao Xin , Liu Yang , Davicioni Elai , Spratt Daniel E. , Sabbioneda Simone , Maga Giovanni , Mucci Lorelei A. , Ghigna Claudia , Marchionni Luigi , Butler Lisa M. , Ellis Leigh , Bordeleau François , Loda Massimo , Vaira Valentina , Labbé David P. , Zadra Giorgia
Published: July 2024

Excel file containing 19 supplementary tables
Supplementary Figure S9 from Obesogenic High-Fat Diet and MYC Cooperate to Promote Lactate Accumulation and Tumor Microenvironment Remodeling in Prostate Cancer
Authors: Boufaied Nadia , Chetta Paolo , Hallal Tarek , Cacciatore Stefano , Lalli Daniela , Luthold Carole , Homsy Kevin , Imada Eddie L. , Syamala Sudeepa , Photopoulos Cornelia , Di Matteo Anna , de Polo Anna , Storaci Alessandra Maria , Huang Ying , Giunchi Francesca , Sheridan Patricia A. , Michelotti Gregory , Nguyen Quang-De , Zhao Xin , Liu Yang , Davicioni Elai , Spratt Daniel E. , Sabbioneda Simone , Maga Giovanni , Mucci Lorelei A. , Ghigna Claudia , Marchionni Luigi , Butler Lisa M. , Ellis Leigh , Bordeleau François , Loda Massimo , Vaira Valentina , Labbé David P. , Zadra Giorgia
Published: July 2024

Supplementary Figure S9 shows GSEA_Hallmark results in human PCa
Supplementary Figure S8 from Obesogenic High-Fat Diet and MYC Cooperate to Promote Lactate Accumulation and Tumor Microenvironment Remodeling in Prostate Cancer
Authors: Boufaied Nadia , Chetta Paolo , Hallal Tarek , Cacciatore Stefano , Lalli Daniela , Luthold Carole , Homsy Kevin , Imada Eddie L. , Syamala Sudeepa , Photopoulos Cornelia , Di Matteo Anna , de Polo Anna , Storaci Alessandra Maria , Huang Ying , Giunchi Francesca , Sheridan Patricia A. , Michelotti Gregory , Nguyen Quang-De , Zhao Xin , Liu Yang , Davicioni Elai , Spratt Daniel E. , Sabbioneda Simone , Maga Giovanni , Mucci Lorelei A. , Ghigna Claudia , Marchionni Luigi , Butler Lisa M. , Ellis Leigh , Bordeleau François , Loda Massimo , Vaira Valentina , Labbé David P. , Zadra Giorgia
Published: July 2024

Supplementary Figure S8 shows migration assays of MYC-CaP cells treated with lactate or LDHA inhibitor FX11.
Supplementary Figure S6 from Obesogenic High-Fat Diet and MYC Cooperate to Promote Lactate Accumulation and Tumor Microenvironment Remodeling in Prostate Cancer
Authors: Boufaied Nadia , Chetta Paolo , Hallal Tarek , Cacciatore Stefano , Lalli Daniela , Luthold Carole , Homsy Kevin , Imada Eddie L. , Syamala Sudeepa , Photopoulos Cornelia , Di Matteo Anna , de Polo Anna , Storaci Alessandra Maria , Huang Ying , Giunchi Francesca , Sheridan Patricia A. , Michelotti Gregory , Nguyen Quang-De , Zhao Xin , Liu Yang , Davicioni Elai , Spratt Daniel E. , Sabbioneda Simone , Maga Giovanni , Mucci Lorelei A. , Ghigna Claudia , Marchionni Luigi , Butler Lisa M. , Ellis Leigh , Bordeleau François , Loda Massimo , Vaira Valentina , Labbé David P. , Zadra Giorgia
Published: July 2024

Supplementary Figure S6 includes scRNA-seq data showing that Luminal (high Ly6d) cells in MYC-transformed DLP display glycolytic features.
Supplementary Figure S2 from Obesogenic High-Fat Diet and MYC Cooperate to Promote Lactate Accumulation and Tumor Microenvironment Remodeling in Prostate Cancer
Authors: Boufaied Nadia , Chetta Paolo , Hallal Tarek , Cacciatore Stefano , Lalli Daniela , Luthold Carole , Homsy Kevin , Imada Eddie L. , Syamala Sudeepa , Photopoulos Cornelia , Di Matteo Anna , de Polo Anna , Storaci Alessandra Maria , Huang Ying , Giunchi Francesca , Sheridan Patricia A. , Michelotti Gregory , Nguyen Quang-De , Zhao Xin , Liu Yang , Davicioni Elai , Spratt Daniel E. , Sabbioneda Simone , Maga Giovanni , Mucci Lorelei A. , Ghigna Claudia , Marchionni Luigi , Butler Lisa M. , Ellis Leigh , Bordeleau François , Loda Massimo , Vaira Valentina , Labbé David P. , Zadra Giorgia
Published: July 2024

Supplementary Figure S2 shows the effect of obesogenic HFD on AP and VP lobes, the effect of HFD on cell proliferation rate in MYC-transformed DLP, and the effect of HFD on WT prostate lobes.
Transforming the Dark into Light: A Siglec-9 Switch
Authors: Abken Hinrich
Published: July 2024

Tumor-associated immune repression dampens the success of T-cell therapy for cancer by a plethora of inhibitory mechanisms including aberrant glycosylation. In this issue, Eisenberg and colleagues show that IFNγ induces hyper-sialylation of cancer cells and that this acts as the “checkpoint” through binding to the inhibitory molecule Siglec-9 on immune cells. A chimeric Siglec-9 “switch” receptor converts the suppressive signal into a stimulatory signal, thereby restoring T-cell responses in the tumor tissue, which has multiple implications for the use of adoptive cell therapy in cancer.

See related article by Eisenberg et al., p. 1380 (3)
Figure S1 from Putrescine Supplementation Limits the Expansion of pks+ Escherichia coli and Tumor Development in the Colon
Authors: Oliero Manon , Cuisiniere Thibault , Ajayi Ayodeji S. , Gerkins Claire , Hajjar Roy , Fragoso Gabriela , Calvé Annie , Vennin Rendos Hervé , Mathieu-Denoncourt Annabelle , Dagbert François , De Broux Éric , Loungnarath Rasmy , Schwenter Frank , Sebajang Herawaty , Ratelle Richard , Wassef Ramses , Richard Carole , Duperthuy Marylise , Gravel Andrée E. , Vincent Antony T. , Santos Manuela M.
Published: July 2024

Figure S1 shows E. coli metabolome and ornithine decarboxylase activity
Figure 3 from Putrescine Supplementation Limits the Expansion of pks+ Escherichia coli and Tumor Development in the Colon
Authors: Oliero Manon , Cuisiniere Thibault , Ajayi Ayodeji S. , Gerkins Claire , Hajjar Roy , Fragoso Gabriela , Calvé Annie , Vennin Rendos Hervé , Mathieu-Denoncourt Annabelle , Dagbert François , De Broux Éric , Loungnarath Rasmy , Schwenter Frank , Sebajang Herawaty , Ratelle Richard , Wassef Ramses , Richard Carole , Duperthuy Marylise , Gravel Andrée E. , Vincent Antony T. , Santos Manuela M.
Published: July 2024

Putrescine decreases EcNC101 expansion and is associated with lower inflammation in mice. A, NF-κB activation in THP1 cells treated with E. coli LPS (1 μL/mL) and putrescine (N = 4; mean ± SEM; ANOVA, post hoc Dunnett compared with cells treated with LPS and 0 mmol/L/mL putrescine). B, Fecal Lcn-2 after DSS-induced flares (mean ± SEM, repeated-measure ANOVA). C, Fecal IL6, (D) TNFα, and (E) IL10 levels at day 56 (Student t test); n.s., nonsignificant; *, P < 0.05; **, P < 0.01. F, EcNC101 CFUs after DSS-induced flares (mean ± SEM, repeated-measure ANOVA). N = 9 per group.
Figure 1 from Putrescine Supplementation Limits the Expansion of pks+ Escherichia coli and Tumor Development in the Colon
Authors: Oliero Manon , Cuisiniere Thibault , Ajayi Ayodeji S. , Gerkins Claire , Hajjar Roy , Fragoso Gabriela , Calvé Annie , Vennin Rendos Hervé , Mathieu-Denoncourt Annabelle , Dagbert François , De Broux Éric , Loungnarath Rasmy , Schwenter Frank , Sebajang Herawaty , Ratelle Richard , Wassef Ramses , Richard Carole , Duperthuy Marylise , Gravel Andrée E. , Vincent Antony T. , Santos Manuela M.
Published: July 2024

Putrescine inhibits the growth of EcNC101. A, Growth of EcNC101 in liquid competition assays with K12 or EcN strains in comparison with the growth of EcNC101 without competition (Ctrl) at each time point (ANOVA, compared with single strain culture of EcNC101 at each time point; N = 4). B, Representative one-dimensional 1H NMR spectra (−0.2–3.5 ppm) of supernatants from EcN, EcK12, EcNC101, and control (LB); sodium (TSP) at 0.0 ppm was the reference peak. Inset images represent putrescine peaks by 1H NMR. C, ODC activity of EcNC101, EcK12, and EcN in minimal medium (M9) with arginine (repeated-measure ANOVA; N = 4). Representative image of the culture media change of color at 32 hours. D, Putrescine concentration measured in the supernatant of EcNC101, EcK12, and EcN grown in M9 in the absence or presence of an increasing concentration of arginine for 7 hours [ANOVA, compared with control (0 mmol/L arginine) of each strain; N = 3]. E, Growth curves of EcNC101 in M9 in the absence or presence of putrescine supplemented at different concentrations (ANOVA, compared with control; N = 4). n.s., nonsignificant; *, P < 0.05; **, P < 0.01; ***, P < 0.001.
The Burden of Hereditary Angioedema in a Large Family in Brazil
Authors: Gehlen Carolina Teló , Mazzeu Juliana Forte , Veronez Camila Lopes , Mendes Agatha Ribeiro , Bertoli Andrezza Fabrízia , Grumach Anete Sevciovic , Pesquero João Bosco , da Silva Jane
Published: July 2024

Introduction: Hereditary angioedema (HAE) is a rare genetic disease characterized by submucosal and subcutaneous edema with high morbidity and possibility of mortality. This study presents the sociodemographic characteristics of a large Brazilian family with HAE. Methods: Descriptive cross-sectional study with patients from two family branches coming from the same city and HAE diagnosis was carried out. Clinical, laboratory, and treatment data of patients have been collected. Genetic testing was performed on some individuals. Correlation tests and comparisons between variables were applied using IBM SPSS Statistics® 2.0 program. Results: We provide a detailed characterization of two families affected by HAE due to C1-INH deficiency, residing in a small town in southern Brazil. These families harbor an identified mutation in the SERPING1 gene (c.1104del, p.Asp369ThrfsTer2). The mean age at HAE diagnosis was 16.7 (±14.0) years, with the mean onset of symptoms at 6.0 (±6.1) years of age. A correlation was observed between patients’ current age and age at HAE diagnosis, with older patients being diagnosed later than younger individuals (p < 0.0001). On average, there were 16.8 emergency visits in the past year (±24.8), and 53.5% of patients reported at least one lifetime hospitalization. Notably, treatment modalities often diverged from consensus recommendations regarding optimal prophylaxis and management of HAE attacks. Conclusions: This study describes one of the largest known families with HAE in Brazil and highlights the significant impact of unfavorable social conditions on disease control.
Emphatic Memories and Their Meaning in Societal and Legal Contexts: A Narrative Review and Position Paper
Authors: Linden Michael , Muschalla Beate
Published: July 2024

Background: Many past and ongoing conflicts in the world are associated with memories. The role of emphatic memories is however often neglected in conflict solving. Therefore, this narrative review gives a short introduction to the phenomenon of emphatic memories and implications for counteracting dysfunctional effects of emphatic memories. Summary: Memory has two connotations. One is remembering and knowing (I can remember when I got married) and on the other is reminding and emphasizing memories (I remind my partner of our wedding day). Memories are less a report on the past but result of current emotions and motives. Emphatic memories serve for self-portrayal and distinction from others, self-exculpation, accusation of others, justification of claims. They are regularly reproachful, have an aggressive character, and are distorted and pseudologic. This is also true on a societal level, as memories are used for defining social groups, and by this for political purposes, in order to juxtapose one group against the other. If memories are revoked, they are regularly accompanied with the very emotions, which were associated with the past event. Corresponding behavior is motivated. Many people suffer from memories and associated emotions and dysfunctional behavior, as is well described in the context of post-traumatic stress disorders. Also, social groups can as a whole suffer from negative emotions because of memories, which may go back up to thousand years. To ensure that memories do not adversely affect individuals and social groups, they should best be forgotten, or at least rescripted, in a way that they are disentangled from negative emotions and motives. An important psychological process in this regard is wisdom and forgiveness, which must not be confused with understanding, justification, tolerating, or reconciliation. Wisdom and forgiveness allow persons to close the books, act self-determined, find freedom from external events, and end suffering because of the past. It is a rational and emotional act. Key Messages: Emphatic memories can cause that individuals and groups do not find peace and persistently provoke new conflicts. Internal and interactional peace can be found if memories are let alone and fade away. Forgiveness and wisdom describe avenues to let dysfunctional memories go.
Three-Dimensional Cell Culture Scaffold Supports Capillary-Like Network Formation by Endothelial Cells Derived from Porcine-Induced Pluripotent Stem Cells
Authors: Liao Yu-Jing , Chen Yi-Shiou , Lin Yu-Ching , Yang Jenn-Rong
Published: July 2024

Introduction: Endothelial cells (EC) can be generated from porcine-induced pluripotent stem cells (piPSC), but poor efficiency in driving EC differentiation hampers their application and efficacy. Additionally, the culture of piPSC-derived EC (piPSC-EC) on three-dimensional (3D) scaffolds has not been fully reported yet. Here, we report a method to improve the generation of EC differentiation from piPSC and to facilitate their culture on 3D scaffolds, providing a potential resource for in vitro drug testing and the generation of tissue-engineered vascular grafts. Methods: We initiated the differentiation of piPSC into EC by seeding them on laminin 411 and employing a three-stage protocol, which involved the use of distinct EC differentiation media supplemented with CHIR99021, BMP4, VEGF, and bFGF. Results: piPSC-EC not only expressed EC markers such as CD31, VE-cadherin, and von Willebrand factor (vWF) but also exhibited an upregulation of EC marker genes, including CD31, CD34, VEGFR2, VE-cadherin, and vWF. They exhibited functional characteristics similar to those of porcine coronary artery endothelial cells (PCAEC), such as tube formation and Dil-Ac-LDL uptake. Furthermore, when cultured on 3D scaffolds, piPSC-EC developed a 3D morphology and were capable of forming an endothelial layer and engineering capillary-like networks, though these lacked lumen structures. Conclusion: Our study not only advances the generation of EC from piPSC through an inhibitor and growth factor cocktail but also provides a promising approach for constructing vascular network-like structures. Importantly, these findings open new avenues for drug discovery in vitro and tissue engineering in vivo.
Emotional Changes during Imagery Rescripting of Aversive Social Memories in Social Anxiety Disorder: A Randomized Controlled Trial
Authors: Seinsche Rosa J. , Fricke Susanne , Neudert Marie K. , Zimmer Raphaela I. , Stark Rudolf , Hermann Andrea
Published: July 2024

Introduction: Imagery rescripting (ImRs) is a psychotherapeutic intervention targeting aversive memories. During the three-phase intervention, patients reexperience their aversive memory (phase 1), observe the scene from their adult perspective, and intervene to help their former selves (phase 2), and reexperience it again with the positive changes (phase 3). Previous studies have rarely investigated emotional and regulatory processes taking place during the intervention. Objective: This randomized controlled trial investigated self-reported affective and physiological responses during ImRs. Methods: Seventy-seven patients with social anxiety disorder (SAD) were randomly assigned to a single session of ImRs or a control intervention (recall and discussion of the memory) targeting an aversive social memory. Heart rate (HR) and heart rate variability (HRV) were assessed during and post hoc ratings of positive and negative feelings after baseline and the intervention phases. Results: Relative to the control intervention, ImRs resulted in an initial increase in negative feelings from baseline to phase 1 and a following larger (phase 1 to phase 2) and more stable (phase 2 to phase 3) decrease in negative feelings/increase in positive feelings. On the physiological level, during ImRs compared to the control intervention, mean HR was significantly higher during phase 1 and HRV during phase 3, each compared to baseline. Conclusions: These results provide further information about the specific sequence of emotional responses on different response levels during ImRs, being consistent with known theories of emotional processing and supposed mechanisms of ImRs.
Nitric Oxide/Glucose Transporter Type 4 Pathway Mediates Cardioprotection against Ischemia/Reperfusion Injury under Hyperglycemic and Diabetic Conditions in Rats
Authors: Al-Kouh Aisha , Babiker Fawzi
Published: July 2024

Introduction: The comorbidities of ischemic heart disease (IHD) and diabetes mellitus (DM) compromise the protection of the diabetic heart from ischemia/reperfusion (I/R) injury. We hypothesized that manipulation of reperfusion injury salvage kinase (RISK) and survivor activating factor enhancement (SAFE) pathways might protect the diabetic heart, and intervention of these pathways could be a new avenue for potentially protecting the diabetic heart. Methods: All hearts were subjected to 30-min ischemia and 30-min reperfusion. During reperfusion, hearts were exposed to molecules proven to protect the heart from I/R injury. The hemodynamic data were collected using suitable software. The infarct size, troponin T levels, and protein levels in hearts were evaluated. Results: Both cyclosporine-A and nitric oxide donor (SNAP) infusion at reperfusion protected 4-week diabetic hearts from I/R injury. However, 6-week diabetic hearts were protected only by SNAP, but not cyclosporin-A. These treatments significantly (p < 0.05) improved cardiac hemodynamics and decreased infarct size. Conclusions: The administration of SNAP to diabetic hearts protected both 4- and 6-week diabetic hearts; however, cyclosporine-A protected only the 4-week diabetic hearts. The eNOS/GLUT-4 pathway executed the SNAP-mediated cardioprotection.
Association of Autoimmune Diseases with the Risk of Parkinson’s Disease
Authors: Ma Yuanzheng , Xiao Yi , Zhang Sirui , Liu Jiyong , Shang Huifang
Published: July 2024

Introduction: PD is a progressive neurodegeneration disease characterized by cardinal motor symptoms such as bradykinesia and tremor. The pathogenesis of PD remains unclear. It is hypothesized that immune system dysfunction may contribute to PD. Thus, autoimmune diseases may influence the risk of incident PD. Methods: We included 398,329 participants without PD at the baseline from UK Biobank. The association between 20 autoimmune diseases with PD was examined using cox hazards regression analyses, adjusting covariates like age, sex, and smoking status in the statistical models. Sensitivity analyses were conducted, adjusting for polygenic risk score and the reported source of PD, to check the robustness. Results: After an average follow-up of 13.1 ± 0.816 years, 2,245 participants were diagnosed with incident PD. After multiple comparison correction, only multiple sclerosis (MS) reached statistical significance and showed an increased risk for incident PD. Compared with non-MS patients, the risk of incident PD in MS patients was 2.57-fold with age and sex being adjusted (95% CI, 1.59–4.14; adjust p value = 0.002). After adjusting lifestyle and other factors, the hazard ratio of incident PD in MS patients was 2.49 (95% CI, 1.55–4.02; adjust p value = 0.004). Excluding the self-reported PD cases in the sensitivity analysis, MS was a detrimental factor for incident PD (HR, 2.06; 95% CI, 1.56–4.05; adjust p value = 0.004). The link between MS and PD did not reach the statistical significance in the sensitivity analysis adjusting the PRS (adjust p value = 0.95). Conclusion: Our study provided evidence from observational analyses that MS was associated with an increased risk of PD. Further investigations should be performed to determine the causal association and potential pathophysiology between MS and PD.
Motor Neuron Disease Population-Based Registry in Egypt: Where Do We Stand?
Authors: Hamdi Nabila , Ocab Omnia , Soliman Radwa , Ludolph Albert , Anwar Wagida , Logroscino Giancarlo , Fahmy Nagia
Published: July 2024

Background: There is a growing body of evidence indicating that the worldwide distribution of amyotrophic lateral sclerosis (ALS) is far from uniform. This is evident through variations in the epidemiology, genetics, and phenotypical characteristics of ALS and other motor neuron diseases (MND) across different regions. However, comprehensive ALS epidemiological studies are still lacking in many parts of the world, especially in Africa. Therefore, we propose the establishment of a population-based register for ALS/MND in Egypt, an important part of Africa with a population of more than 100 millions of people. Summary: Given Egypt’s distinctive social and demographic characteristics, it is highly recommended to employ specific, recently developed epidemiological techniques for assessing the prevalence and incidence of these diseases within the country. By utilizing these methods, we can gather invaluable data that will contribute to a deeper understanding of ALS and enable us to effectively address its impact on the population of Egypt. Key Messages: Our goal with this pioneering ALS/MND population-based register in Egypt is to define the burden of ALS in this part of Africa and to increase the chances for this consanguineous population to get access to modern individualized genetic therapies. Additionally, we aspire to uncover potential environmental factors and gene-environment interactions that contribute to the development of ALS. This knowledge of MND individual and group risk in Egypt will not only open doors for interventions but also provide opportunities for future research and discovery.
Prevalence and Rapid Screen Method of Diagnostic Criteria for Psychosomatic Research Syndromes in Human Papillomavirus-Infected Patients
Authors: Cui Xuelian , Ding Lixin , Xu Yongjuan , Yuan Xiaosong , Zhang Qiaoli , Rafanelli Chiara , Gostoli Sara , Liu Zhiwei , Cao Jianxin
Published: July 2024

Introduction: The early and rapid identification of psychosomatic symptoms is crucial to prevent harmful outcomes in patients with human papillomavirus (HPV) infection in busy comprehensive clinics. This study aimed to explore the prevalence and rapid screening method of the Diagnostic Criteria for Psychosomatic Research-revised (DCPR) syndromes in patients with HPV infection. Methods: A total of 504 participants underwent a clinical assessment that included DCPR, Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5), the Social Support Rating Scale (SSRS), the Simplified Coping Style Questionnaire (SCSQ), fear of disease, sociodemographic and clinical characteristics. The prevalence of DCPR syndromes and DSM-5 diagnoses were compared between the HPV-positive and negative patients using χ2 tests. We explored the rapid screen indicator through multiple logistic regression analyses of the participants’ psychosocial factors, sociodemographic and clinical characteristics. Results: The incidence of DCPR syndromes in HPV-positive patients (56.6%) was significantly greater than that in HPV-negative patients (17.3%) and DSM-5 diagnoses (8.5%) in the HPV-positive group. Health anxiety, irritable mood, type A behavior, and demoralization were the most common psychosomatic syndromes in HPV-positive patients. As the degree of fear increased from 0 to 5 to 10, the risk of DCPR increased from 1.27 (95% CI: 0.21–7.63) to 3.24 (score range: 1–5, 95% CI: 1.01–10.39) to 9.91 (score range: 6–10, 95% CI: 3.21–30.62) in the HPV-positive group. Conclusion: The degree of fear, as an independent risk factor, could be used to quickly screen outpatients with a high risk of DCPR syndrome among women with HPV infection.
The Efficacy of the Herbal Formula of Bunium persicum and Coriandrum sativum on Clinical Symptoms of Patients with Functional Dyspepsia: A Double-Blind Randomized Controlled Trial
Authors: Azimi Maryam , Esfandiarpour Mahboobeh , Raeiszadeh Mahboobeh , Salajegheh Faranak , Saeidpour Parizi Ali
Published: July 2024

Introduction: Functional dyspepsia (FD) is one of the most prevalent chronic disorders affecting up to 30% of the world population with considerable impairment of quality of life. This study evaluated the efficacy of the herbal preparation of Bunium persicum (Boiss.) B.Fedtsch. and Coriandrum sativum L. on symptom severity, symptom frequency, and quality of life of patients with FD. Methods: This double-blind randomized controlled clinical trial, with parallel groups allocation ratio of 1:1, was conducted in a referral clinic of Afzalipour Hospital affiliated with Kerman University of Medical Sciences in Kerman, southeastern Iran. A total of 90 patients with FD (diagnosed based on the Rome IV criteria) were included in this study. The patients with complications during the intervention, pregnancy or lactation, a history of allergy to herbal drugs, use of other medication that affect the symptoms of FD during the study, and severe organic or psychiatric disorders were excluded. The participants received one capsule containing 500 mg of herbal preparation or placebo twice a day for 4 weeks and were subsequently followed up for 4 more weeks. Clinical outcomes were assessed via the Dyspepsia Severity Questionnaire, the Rome IV Diagnostic Questionnaire, and Nepean Dyspepsia Index Questionnaire. Results: A total 40 participants in each group completed the follow-up period, and their data were analyzed statistically. All clinical outcomes showed significant improvements by herbal preparation compared to the placebo without serious side effects (p < 0.05). Conclusions: This herbal preparation can significantly improve the quality of life, and symptoms of FD compared to placebo.
Surgical Complications in Subthalamic Nucleus Deep Brain Stimulation for Parkinson’s Disease: Experience in 800 Patients
Authors: Holewijn Rozemarije A. , Wiggerts Yarit , Bot Maarten , Verbaan Dagmar , de Bie Rob M.A. , Schuurman Rick , van den Munckhof Pepijn
Published: July 2024

Introduction: We present our surgical complications resulting in neurological deficit or additional surgery during 25 years of DBS of the subthalamic nucleus (STN) for Parkinson’s disease (PD). Methods: We conducted a retrospective chart review of all PD patients that received STN DBS in our DBS center between 1998 and 2023. Outcomes were complications resulting in neurological deficit or additional surgery. Potential risk factors (number of microelectrode recording tracks, age, anesthesia method, hypertension, and sex) for symptomatic intracerebral hemorrhage (ICH) were analyzed. Furthermore, lead fixation techniques were compared. Results: Eight hundred PD patients (507 men, 293 women) received unilateral (n = 11) or bilateral (n = 789) implantation of STN electrodes. Neurological deficit due to ICH, edema, delirium, or infarction was seen in 8.4% of the patients (7.4% transient, 1.0% permanent). Twenty-two patients (2.8%) had a symptomatic ICH following STN DBS, for which we did not find any risk factors, and five had permanent sequelae due to ICH (0.6%). Of all patients, 18.4% required additional surgery; the proportion was reduced from 27% in the first 300 cases to 13% in the last 500 cases (p < 0.001). The infection rate was 3.5%, which decreased from 5.3% in the first 300 cases to 2.2% in the last 500 cases. The use of a lead anchoring device led to significantly less lead migrations than miniplate fixation. Conclusion: STN DBS leads to permanent neurological deficit in a small number of patients (1.0%), but a substantial proportion needs some additional surgical procedure after the first DBS system implantation. The risk of revision surgery was reduced over time but remained significant. These findings need to be discussed with the patient in the preoperative informed consent process in addition to the expected health benefit.
Patient-Reported Satisfaction with Hair Regrowth in a Study of Ritlecitinib in Alopecia Areata: Results from ALLEGRO-2b/3
Authors: Sinclair Rodney , Law Ernest H. , Zhang Xingqi , Zhang Fan , Napatalung Lynne , Zwillich Samuel H. , King Brett , Mesinkovska Natasha
Published: July 2024

Introduction: Patients with alopecia areata (AA) report high levels of dissatisfaction with commonly used treatments. Patient-reported outcomes are essential to understanding patients’ experiences with AA treatments. The objective of this study was to evaluate patient-reported satisfaction with hair growth among patients with AA receiving ritlecitinib or placebo and the correlation between clinician-assessed efficacy and patient-reported satisfaction. Methods: In the ALLEGRO-2b/3 (NCT03732807) trial, patients with AA and ≥50% scalp hair loss were randomized to daily ritlecitinib or placebo for 24 weeks, with a 24-week extension of continued ritlecitinib or switch from placebo to ritlecitinib. The Patient Satisfaction with Hair Growth (P-Sat) measure evaluated patients’ satisfaction with hair growth in 3 domains: amount, quality, and overall satisfaction with hair growth. The prespecified analysis evaluated the proportion of patients who were slightly, moderately, or very satisfied with hair growth. Several post hoc analyses assessed the proportion of patients who were moderately/very satisfied and moderately/very dissatisfied and calculated polyserial correlations between change from baseline (CFB) in Severity of Alopecia Tool (SALT) and P-Sat scores at weeks 24 and 48. Results: At week 24, the proportion of patients (N = 718) reporting satisfaction (slightly, moderately, or very satisfied) overall with their hair growth ranged from 36.4% in the ritlecitinib 10-mg group (evaluated for dose ranging only) to 67.5% in the 200/50-mg group versus 22.6% in the placebo groups. In patients randomized to ritlecitinib, the proportion who were satisfied increased or was maintained at week 48. A substantially greater proportion of placebo patients who switched to ritlecitinib reported satisfaction at week 48 than at week 24. Similar results were observed for patient satisfaction with the amount and quality of hair growth. In the post hoc analyses defining satisfaction as moderately/very satisfied and dissatisfaction as moderately/very dissatisfied, the benefit of ritlecitinib was also observed. All P-Sat domain scores strongly correlated with CFB-SALT scores at weeks 24 (range 0.73–0.76; p < 0.05) and 48 (0.74–0.77; p < 0.05). Conclusions: Patients receiving active ritlecitinib doses reported favorable results versus placebo in satisfaction with hair growth up to week 48. High concordance was observed between improvement in scalp hair growth evaluated by clinicians and patient-reported satisfaction.
Chronic Rhinosinusitis Risk after Maxillectomy with Microvascular Reconstruction
Authors: Werner Michael T. , Carey Ryan M. , Panara Kush , Harris Jacob , Tasche Kendall K. , Brody Robert M. , Rajasekaran Karthik , Palmer James N. , Adappa Nithin D. , Newman Jason G. , Shanti Rabie M. , Cannady Steven B.
Published: July 2024

Introduction: Chronic rhinosinusitis (CRS) can be associated with tumors involving the maxillary sinus, but outcomes after undergoing maxillectomy with free flap reconstruction remain unclear. Methods: A retrospective analysis of medical records was performed to evaluate evidence of CRS in patients who underwent maxillectomy with free flap reconstruction at a single tertiary care academic institution from 2013 through 2020. Results: Eighty-four patients were assessed. Nineteen (22.6%) patients were diagnosed with CRS after surgery, 23 (27.4%) patients were treated for sinus symptoms, and 49 (58.3%) had radiographic evidence of sinus inflammation for more than 6 months. Risk factors for requiring sinus treatment included adjuvant or neoadjuvant chemotherapy (p = 0.002) and pre-operative use of sinus medication (p < 0.001). Radiographic evidence of sinusitis 6 months after surgery is also closely associated with sinusitis treatment (p = 0.051). Conclusions: CRS may be underdiagnosed in patients undergoing maxillectomy with microvascular reconstruction. Further evaluation into patient sinus disease and symptoms following neoplastic surgery may lead to a higher quality of life in some long-term survivors.
Epidemic Intelligence Threat Reporting Profile in Portugal during the COVID-19: 2 Years of Decrease in Reporting on Non-COVID-19 Threats
Authors: Ricoca Peixoto Vasco , Grau-Pujol Berta , Ourique Matilde , Lourenço da Silva Renato , Ferreira Mariana , Firme Ana , Sentís Alexis , Vasconcelos Paula
Published: July 2024

Background: Epidemic intelligence (EI) ensures early detection, assessment, and communication of public health threats. Threat reporting defines priorities and mobilize resources for surveillance, prevention, and control. In Portugal, the Directorate-General of Health (DGS) is responsible for EI and publishes a weekly public health threat report (RONDA). Changes in threats in regular threat reports since COVID-19 have not been previously described. We analysed changes in non-COVID threat reporting in the weekly threat report. Methods: Using the DGS Emergency Operations Centre’s threat reporting database, we compared threats reported in RONDAs from 2016 to 2022 in three sequential periods: P1 before COVID-19 (January 2016–March 2020), P2 during acute COVID-19 restrictions (April 2020–February 2022), and P3 in post-acute COVID-19 phase (February 2022–September 2022). We described the monthly average frequency of reports on non-COVID-19 threats in those periods considering different disease groups, geographical focus, and information sources. We estimated expected non-COVID-19 reports on threats using a forecast model fitted to the time series until March 2020 and compared observed and expected values. Results: Non-COVID-19 threats had a decrease in the monthly average frequency of reporting in period 2 (x¯1: 4.7 vs. x¯: 2.3, p < 0.001) compared to period 1. Using the forecast methods, there were 114 fewer non-COVID threats than the 162 expected (−70%) in period 2. In period 3, there were 105 more threats than expected (+256%). The ECDC and the WHO were the most frequent sources of information followed by national Public Health sources. Conclusions: During COVID-19, there was a decrease in reports on non-COVID threats in Portugal. COVID-19 possibly affected global EI, by shifting attention and resources from other threats to the pandemic. However, the number of threats that warrant follow-up and communication is increasing. Further research is necessary to inform the EI research and development agenda, to ensure that all relevant threats are detected, accessed, and communicated according to evolving EI objectives and priorities while resources and preparedness are guaranteed.
Combined Resection of Liver and Hilar Bifurcation for Colorectal Liver Metastasis: A Single-Center Experience and Review of the Literature
Authors: Hiller Sebastian Daniel , Baumgart Janine , Gerber Tiemo , Straub Beate Katharina , Lang Hauke
Published: July 2024

Introduction: Colorectal liver metastases (CRLM) infiltrating the hilar bifurcation is rarely described. We investigated the outcome of partial hepatectomy combined with resection of the hilar bifurcation. Methods: Data collection for patients who underwent resection for CRLM at our institution was performed prospectively from January 2008 to August 2021. Follow-up ended in August 2023. Patients with and without bile duct infiltration of CRLM were analyzed retrospectively. The primary endpoints were overall (OS) and recurrence-free survival (RFS). Results: A total of 1,156 liver resections were screened. Out of those, 18 were combined resections of the liver and the hilar bifurcation. Bile duct infiltration of CRLM was histologically proven in 5 of 18 cases. Preoperative mild obstructive jaundice occurred in 6 of 18 patients and was treated by drainage. Out of those, only 2 had a confirmed infiltration of the hilar bifurcation by CRLM. The median recurrence-free survival (RFS) was 10 months in those patients with bile duct infiltration compared to 9 months in those with no infiltration (p = 0.503). Conclusion: While CRLM is common, infiltration into the central biliary tract is rare. Tumor invasion of the biliary tree can cause jaundice, but jaundice does not necessarily mean tumor invasion. We have shown that combined resection of the liver and hilar bifurcation for CRLM is safe and infiltration of the bile duct by CRLM did not seem to have a significant effect on RFS or OS.
Reduction of Postoperative Complications in Pancreatic Surgery by Standardizing Perioperative Management: An Observational Cohort Study
Authors: Herzberg Jonas , Strate Tim , Acs Miklos , Piso Pompiliu , Guraya Salman Yousuf , Honarpisheh Human
Published: July 2024

Introduction: Resection for pancreatic malignancy remains the gold standard for cure. Postoperative morbidity continues to be high even after technical innovations. This study evaluates the effectiveness of a standard perioperative pancreatic oncological surgery step-by-step protocol in reducing organ-specific complications. Methods: In this observational cohort study, we analyzed the outcomes of oncologic pancreatic head resections from 2015 to 2022 after the implementation of a standard perioperative fail-safe protocol and compared these data with a historical cohort (2013–2014). In the study group, all patients were treated with preoperative limited mechanical bowel preparation, administration of a somatostatin analog, and a “pancreatic duct tube” in pancreatoduodenectomy. The primary outcome measure was the occurrence of postoperative organ-specific complications. Results: A total of 151 patients were included in this study. The rate of postoperative pancreatic fistula (grade B and C) in the fail-safe group was 4.2%. Other organ-specific complications as postoperative hemorrhage (2.5%) and delayed gastric emptying (9.2%) also occurred less frequent than before implementation of the fail-safe protocol. Conclusion: The use of this standardized fail-safe protocol for oncologic pancreatoduodenectomy can lead to a low postoperative morbidity with improved surgical outcomes.
Carbapenem-Resistant Enterobacteriaceae Colonization or Infection Was Not Associated with Post-Liver Transplant Graft Failure: An Observational Cohort Study
Authors: Caria João , Gonçalves Ana C. , Cristóvão Gonçalo , Carlos Maria , Magalhães Sara , Almeida Vasco , Moreno Fernanda , Mateus Élia , Pinheiro Hélder , Póvoas Diana , Maltez Fernando M.T. , Perdigoto Rui , S. Cardoso Filipe , P. Marques Hugo
Published: July 2024

Introduction: Carbapenem-resistant Enterobacteriaceae (CRE) epidemiology among liver transplant (LT) recipients is variable. We studied the impact of CRE colonization and infection on LT recipients’ outcomes. Methods: This observational cohort study included consecutive adult LT recipients between January 2019 and December 2020 at Curry Cabral Hospital, Lisbon, Portugal. Primary exposures were CRE colonization (rectal swabs under a screening program) and infection within 1 year of index LT. Primary endpoint was graft failure within 1 year of the index LT. Results: Among 209 patients, the median (interquartile range [IQR]) age was 57 (47–64) years and 155 (74.2%) were male. CRE colonization was identified in 28 (13.4%) patients during the first year posttransplant (median [IQR] number of rectal swabs per patient of 4 [2–7]). CRE resistance genes identified were OXA48 in 8 (3.6%) patients, KPC in 19 (67.9%) patients, and VIM in 1 (3.6%) patient. Any bacterial/fungal and CRE infections were diagnosed in 88 (42.1%) and 6 (2.9%) patients, respectively, during the first year posttransplant. After adjusting for confounders, neither CRE colonization (aOR [95% CI] = 1.83 [0.71–4.70]; p = 0.21) nor infection (aOR [95% CI] = 1.35 [0.17–11.06]; p = 0.78) was associated with graft failure within 1 year of index LT. Discussion/Conclusion: Under a screening program, CRE colonization and infection prevalence was low and neither was associated with graft failure.
Test-Retest Reliability of Movement Displacement during a 20-s Stepping-in-Place Test in Community-Dwelling Older Adults with and without Supportive Care
Authors: Fujita Eiji , Takeshima Nobuo , Sato Hideto , Kohama Takeshi , Kusunoki Masanobu , Oba Yukiya , Brechue William F.
Published: July 2024

Introduction: Our recent reports have shown that movement pattern and displacement assessed with an infrared depth sensor during a 20-s stepping-in-place test (ST) correlates with measures of balance and need for assistance in older individuals. This study investigated ST test-retest reliability in community-dwelling older adults with and without supportive care. Methods: Two groups were included: those not participating (HO: n = 25, 74.7 ± 5.2 years) and those participating (DSU: n = 41, 78.8 ± 5.8 years) in regular senior day services (supportive care). HO completed three ST trials, separated by 1 week, while DSU completed two ST trials during the same half-day supportive care visit. Testing was conducted with eyes open. ST measures included head movement path distance (TMD), maximum movement displacement (MMD), knee movement path length (KMD), and stepping rate (STEP). TMD×KMD−1 ratio indicated upper-body sway relative to lower-body. Test-retest reliability (intra-class correlation coefficients, ICCs) and between-trial and between group differences (ANCOVA, adjusting for age) were assessed. Results: After adjusting for age, TMD, KMD, TMD×KMD−1 were lesser and STEP was greater in HO than DUS. HO ST variables did not differ across testing days. HO ICC (1, 3) for TMD (0.911 [95% confidence interval: 0.827–0.958]), MMD (0.918 [0.814–0.961]), KMD (0.838 [0.685–0.923]), and TMD×KMD−1 (0.940 [0.884–0.872]) showed strong to very strong reliability. Similarly, DSU ST variables did not differ across same day trials and ICC (1, 2) for TMD, KMD, and TMD×KMD−1 displayed very strong reliability. Conclusion: These ST variables exhibited excellent test-retest reliability of discriminating between community-dwelling older adults with and without supportive care.
Experience and Prognostic Analysis with Avelumab Switch Maintenance Treatment in Metastatic Urothelial Carcinoma
Authors: Isobe Teruki , Naiki Taku , Sugiyama Yosuke , Naiki-Ito Aya , Nagai Takashi , Etani Toshiki , Iida Keitaro , Noda Yusuke , Shimizu Nobuhiko , Aoki Maria , Gonda Masakazu , Morikawa Toshiharu , Banno Rika , Kubota Hiroki , Ando Ryosuke , Kawai Noriyasu , Yasui Takahiro
Published: July 2024

Introduction: Avelumab (Ave) is approved for metastatic urothelial carcinoma (mUC) maintenance therapy and prolongs overall survival (OS). We explored trends related to Ave treatment of mUC patients. Methods: A total of 72 patients with mUC treated with first-line chemotherapy, from January 2019 to November 2022, at our affiliated institutions, were analyzed. We compared clinical parameters and the prognosis of patients treated with Ave (n = 43) because of progression during first-line chemotherapy, with untreated patients (Ave-untreated; n = 29). Among the Ave-treated group, we classified patients showing a complete or partial response or stable disease in their best response to Ave maintenance therapy as Ave-suitable patients; these were retrospectively analyzed. Potential prognostic factors, including the Geriatric Nutritional Risk Index (GNRI) for determining patients suitable for Ave, were evaluated. Results: The basic clinical parameters of patients when first-line treatment was initiated were not statistically different between the two groups. The Ave-suitable group (median 26.6 months, 95% confidence interval [CI]: 19.4–not reached [NR]) showed significantly longer median OS after first-line treatment than the Ave-untreated group (median 12.0 months, 95% CI: 7.5–NR) with tolerable adverse events. The cut-off values of prognostic factors were set by the receiver operating characteristic curve. Low age and GNRI sustainability were revealed as significant prognostic factors for being Ave-suitable both in univariate and multivariate analysis. Conclusion: In mUC, Ave maintenance prolonged OS within tolerable safety profiles. GNRI sustainability may be used as a biomarker to predict being Ave-suitable.
Functional Characterization of Thyroid Peroxidase Missense Variants Causing Thyroid Dyshormonogenesis in Asian Indian Population
Authors: Sarma Asodu Sandeep , Desai Ankush , Rao Madhava , Sahoo Jaya Prakash , Shivaprasad Channabasappa , Ranganath Prajnya , Lakshmi Pragna , D’Sa Lorraine , Dalal Ashwin
Published: July 2024

Introduction: Thyroid dyshormonogenesis (TDH) is a subgroup of congenital hypothyroidism with recessive inheritance resulting from disease-causing variants in thyroid hormone biosynthesis pathway genes, like DUOX2, TG, TPO, SLC5A5, SLC26A4, IYD, DUOXA2, and SLC26A7. Thyroid peroxidase (TPO) is a crucial enzyme involved in thyroid hormone biosynthesis and is one of the frequently mutated genes in patients with TDH. The purpose of the study was to describe the in silico and functional characterization of novel variants in TPO gene identified in patients with TDH. Methods: We performed exome sequencing in Indian patients with TDH. In the current study, we describe the results of patients with TPO gene mutations. Exome sequencing results were further analysed by Sanger sequencing, computational studies, and in vitro functional studies such as immunofluorescence and enzyme assay. Results: We identified nine biallelic disease-causing variants in the TPO gene in 12 patients from nine unrelated Indian families. Eight of the nine variants were novel. No recurrent variants were identified. Computational analysis of six missense variants showed that these amino acid substitutions caused changes in non-covalent interactions with the adjacent residues that may affect the TPO protein structure and function. In vitro experimental data using immunofluorescence assay showed that these variants did not affect the plasma membrane localization of the TPO protein but caused a significant loss of TPO enzymatic activity compared to the wild type. Conclusion: Our study revealed multiple novel pathogenic variants in TPO gene in Indian patients, thereby expanding the genotype spectrum. Functional studies helped us to reveal the pathogenicity of the missense variants.