bluuebunny/crossref_metadata_2025 huggingface dataset:
Selinexor in Combination with R-CHOP for Frontline Treatment of Non-Hodgkin Lymphoma: Results of a Phase I Study
Authors: Seymour Erlene K. , Khan Husain Yar , Li Yiwei , Chaker Mahmoud , Muqbil Irfana , Aboukameel Amro , Ramchandren Radhakrishanan , Houde Christiane , Sterbis Golbon , Yang Jay , Bhutani Divaya , Pregja Silvana , Reichel Kathy , Huddlestun Amy , Neveux Colleen , Corona Kelly , Landesman Yosef , Shah Jatin , Kauffman Michael , Shacham Sharon , Mohammad Ramzi M. , Azmi Asfar S. , Zonder Jeffrey A.
Published: March 2021

Purpose:

The nuclear exporter protein exportin-1 (XPO1) is overexpressed in non-Hodgkin lymphoma (NHL) and correlates with poor prognosis. We evaluated enhancing R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) activity in NHL by targeted inhibition of XPO1 using the selective inhibitor of nuclear export (SINE) compounds.

Patients and Methods:

We evaluated the antitumor activity of SINE compounds in combination with CHO chemotherapy in vitro and in vivo. Newly diagnosed NHL patients in a phase I dose-escalation study received R-CHOP for 6 cycles with weekly selinexor (60, 80, and 100 mg), then selinexor maintenance therapy for one year. RT-PCR, Western blotting, and RNA sequencing were performed on patient blood samples.

Results:

SINE compounds synergized with CHO in vitro in NHL cell lines and in vivo in our murine xenograft model. In our phase I study, selinexor was dosed at 60 mg (n = 6) and 80 mg (n = 6). The most common adverse events (AE) among 12 patients were fatigue (67%) and nausea (100%). Grade 3–4 AEs were infrequent. Ten evaluable patients had an overall response rate of 100% and complete remission rate of 90% with sustained remissions (median follow-up: 476 days). Maximally tolerated dose was not reached; however, the recommended phase II dose was 60 mg selinexor weekly after evaluating tolerability and discontinuation rates for each dose cohort. Analysis of patient blood samples revealed downregulation of XPO1 and several prosurvival markers.

Conclusions:

SINE compounds enhance the activity of CHO in vitro and in vivo. Selinexor in combination with R-CHOP was generally well tolerated and showed encouraging efficacy in NHL (NCT03147885).
Targeting Ovarian Cancer Stem Cells by Dual Inhibition of HOTAIR and DNA Methylation
Authors: Wang Weini , Fang Fang , Ozes Ali , Nephew Kenneth P.
Published: March 2021

Ovarian cancer is a chemoresponsive tumor with very high initial response rates to standard therapy consisting of platinum/paclitaxel. However, most women eventually develop recurrence, which rapidly evolves into chemoresistant disease. Persistence of ovarian cancer stem cells (OCSCs) at the end of therapy has been shown to contribute to resistant tumors. In this study, we demonstrate that the long noncoding RNA HOTAIR is overexpressed in HGSOC cell lines. Furthermore, HOTAIR expression was upregulated in OCSCs compared with non-CSC, ectopic overexpression of HOTAIR enriched the ALDH+ cell population and HOTAIR overexpression increased spheroid formation and colony-forming ability. Targeting HOTAIR using peptide nucleic acid-PNA3, which acts by disrupting the interaction between HOTAIR and EZH2, in combination with a DNMT inhibitor inhibited OCSC spheroid formation and decreased the percentage of ALDH+ cells. Disrupting HOTAIR-EZH2 with PNA3 in combination with the DNMTi on the ability of OCSCs to initiate tumors in vivo as xenografts was examined. HGSOC OVCAR3 cells were treated with PNA3 in vitro and then implanted in nude mice. Tumor growth, initiation, and stem cell frequency were inhibited. Collectively, these results demonstrate that blocking HOTAIR–EZH2 interaction combined with inhibiting DNA methylation is a potential approach to eradicate OCSCs and block disease recurrence.
Expanding the Repertoire for “Large Small Molecules”: Prodrug ABBV-167 Efficiently Converts to Venetoclax with Reduced Food Effect in Healthy Volunteers
Authors: Salem Ahmed Hamed , Tao Zhi-Fu , Bueno Orlando F. , Chen Jie , Chen Shuang , Edalji Rohinton , Elmore Steven W. , Fournier Keith M. , Harper Kaid C. , Hong Richard , Jenkins Gary J. , Ji Jianguo , Judge Russell A. , Kalvass John C. , Klix Russell C. , Ku Yi-Yin , Leverson Joel D. , Marks Richard A. , Marsh Kennan C. , Menon Rajeev M. , Park Chang H. , Phillips Darren C. , Pu Yu-Ming , Rosenberg Saul H. , Sanzgiri Yeshwant D. , Sheikh Ahmad Y. , Shi Yi , Stolarik Deanne , Suleiman Ahmed A. , Wang Xilu , Zhang Geoff G.Z. , Catron Nathaniel D. , Souers Andrew J.
Published: March 2021

Since gaining approval for the treatment of chronic lymphocytic leukemia (CLL), the BCL-2 inhibitor venetoclax has transformed the treatment of this and other blood-related cancers. Reflecting the large and hydrophobic BH3-binding groove within BCL-2, venetoclax has significantly higher molecular weight and lipophilicity than most orally administered drugs, along with negligible water solubility. Although a technology-enabled formulation successfully achieves oral absorption in humans, venetoclax tablets have limited drug loading and therefore can present a substantial pill burden for patients in high-dose indications. We therefore generated a phosphate prodrug (3, ABBV-167) that confers significantly increased water solubility to venetoclax and, upon oral administration to healthy volunteers either as a solution or high drug-load immediate release tablet, extensively converts to the parent drug. Additionally, ABBV-167 demonstrated a lower food effect with respect to venetoclax tablets. These data indicate that beyond-rule-of-5 molecules can be successfully delivered to humans via a solubility-enhancing prodrug moiety to afford robust exposures of the parent drug following oral dosing.
Kidney Injury Molecule-1 and Periostin Urinary Excretion and Tissue Expression Levels and Association with Glomerular Disease Outcomes
Authors: Wu Qiaoyan , Troost Jonathan P. , Dai Tiane , Nast Cynthia , Eddy Sean , Wei Boxian , Wang Ying , Gipson Debbie S. , Dell Katherine M. , Gibson Keisha L. , Kretzler Matthias , Adler Sharon
Published: March 2021

Introductions: Kidney injury molecule-1 (KIM-1) and periostin (POSTN) are proximal and distal tubule injury biomarkers. We tested whether baseline urine KIM-1/Cr (uKIM-1/Cr) and/or uPOSTN/Cr correlated with disease severity or improved a remission prediction model. Methods: Baseline uKIM-1/Cr and uPOSTN/Cr were measured on spot urine samples from immunosuppression-free patients enrolled in Nephrotic Syndrome Study Network until December 15, 2014. Urine protein/Cr (UPCR) and albumin/Cr (UACR) were measured at baseline, 4 months, and until last follow-up. Glomerular and tubulointerstitial (TI) expression arrays were analyzed from a baseline research renal biopsy core collected during a clinically indicated biopsy. Renal diagnoses were centrally confirmed, sections scanned, and measured morphometrically. Correlations between baseline uKIM-1/Cr and uPOSTN/Cr and UPCR, UACR, histopathologic features, glomerular and TI KIM-1 and POSTN expression levels, and renal outcomes were assessed. Results: Baseline uKIM-1/cr correlated with UPCR and UACR and were associated with complete remission (CR) after adjustment for proteinuria, histopathologic diagnosis, and treatment. Baseline uKIM-1/Cr also correlated with degree of foot process effacement and acute tubular injury. Glomerular and TI KIM-1 expression levels correlated with UPCR and UACR. Higher TI KIM-1 expression levels correlated with interstitial fibrosis, tubular atrophy, and global glomerulosclerosis, while glomerular KIM-1 expression correlated with time to remission. Findings for POSTN were of lesser statistical strength. Discussion/Conclusion: Lower baseline uKIM-1/Cr values were associated with more rapid time to CR after adjusting for proteinuria, histopathologic diagnosis, and treatment. Increased TI KIM-1 expression levels in proteinuric states were associated with chronic morphological injury; lower glomerular expression levels were associated with a greater potential for proteinuria reversibility.
The Truncated Splice Variant of the Granulocyte-Macrophage-Colony-Stimulating Factor Receptor β- Chain in Peripheral Blood Serves as Severity Biomarker of Respiratory Failure in Newborns
Authors: Schulte Verena , Sipol Alexandra , Burdach Stefan , Rieger-Fackeldey Esther
Published: March 2021

Background: The granulocyte-macrophage-colony-stimulating factor (GM-CSF) plays an important role in surfactant homeostasis. βC is a subunit of the GM-CSF receptor (GM-CSF-R), and its activation mediates surfactant catabolism in the lung. βIT is a physiological, truncated isoform of βC and is known to act as physiological inhibitor of βC. Objective: The aim of this study was to determine the ratio of βIT and βC in the peripheral blood of newborns and its association with the degree of respiratory failure at birth. Methods: We conducted a prospective cohort study in newborns with various degrees of respiratory impairment at birth. Respiratory status was assessed by a score ranging from no respiratory impairment (0) to invasive respiratory support (3). βIT and βC expression were determined in peripheral blood cells by real-time PCR. βIT expression, defined as the ratio of βIT and βC, was correlated with the respiratory score. Results: βIT expression was found in all 59 recruited newborns with a trend toward higher βIT in respiratory ill (score 2, 3) newborns than respiratory healthy newborns ([score 0, 1]; p = 0.066). Seriously ill newborns (score 3) had significantly higher βIT than healthy newborns ([score 0], p = 0.010). Healthy preterm infants had significantly higher βIT expression than healthy term infants (p = 0.019). Conclusions: βIT is expressed in newborns with higher expression in respiratory ill than respiratory healthy newborns. We hypothesize that βIT may have a protective effect in postnatal pulmonary adaptation acting as a physiological inhibitor of βC and, therefore, maintaining surfactant in respiratory ill newborns.
Ventilation Heterogeneity in Asthma and COPD: The Value of the Poorly Communicating Fraction as the Ratio of Total Lung Capacity to Alveolar Volume
Authors: Pisi Roberta , Aiello Marina , Calzetta Luigino , Frizzelli Annalisa , Alfieri Veronica , Bertorelli Giuseppina , Pisi Giovanna , Chetta Alfredo
Published: March 2021

Background: The ventilation heterogeneity (VH) is reliably assessed by the multiple-breath nitrogen washout (MBNW), which provides indices of conductive (Scond) and acinar (Sacin) VH as well as the lung clearance index (LCI), an index of global VH. VH can be alternatively measured by the poorly communicating fraction (PCF), that is, the ratio of total lung capacity by body plethysmography to alveolar volume from the single-breath lung diffusing capacity measurement. Objectives: Our objective was to assess VH by PCF and MBNW in patients with asthma and with COPD and to compare PCF and MBNW parameters in both patient groups. Method: We studied 35 asthmatic patients and 45 patients with COPD. Each patient performed spirometry, body plethysmography, diffusing capacity, and MBNW test. Results: Compared to COPD patients, asthmatics showed a significantly lesser degree of airflow obstruction and lung hyperinflation. In asthmatic patients, both PCF and LCI and Sacin values were significantly lower than the corresponding ones of COPD patients. In addition, in both patient groups, PCF showed a positive correlation with LCI (p < 0.05) and Sacin (p < 0.05), but not with Scond. Lastly, COPD patients with PCF >30% were highly likely to have a value ≥2 of the mMRC dyspnea scale. Conclusions: These results showed that PCF, a readily measure derived from routine pulmonary function testing, can provide a comprehensive measure of both global and acinar VH in asthma and in COPD patients and can be considered as a comparable tool to the well-established MBNW technique.
Comparison of Thulium Laser Resection of Bladder Tumors and Conventional Transurethral Resection of Bladder Tumors for Non-Muscle-Invasive Bladder Cancer
Authors: Liu Zheng , Zhang Yucong , Sun Guoliang , Ouyang Wei , Wang Shen , Xu Hao , Hu Henglong , Li Fan , Yang Jun , Wang Zhihua , Guan Wei , Yu Xiao , Hu Zhiquan , Chen Zhong , Wang Shaogang , Long Gongwei , Li Heng
Published: March 2021

Introduction: The thulium laser resection of bladder tumors (TmLRBT) was increasingly used in the treatment of non-muscle-invasive bladder cancer (NMIBC) recently, and here we report the relevant outcomes of our institution to evaluate its efficacy and safety. Methods: We retrospectively collected the data of NMIBC patients who underwent either TmLRBT or transurethral resection of bladder tumor (TURBT). The baseline characteristics and perioperative outcomes were compared in these 2 groups. Results: The TmLRBT had a higher rate of detrusor identification than TURBT (97.4 vs. 87.6%, p = 0.001). After screening, 134 patients who underwent TmLRBT and 152 patients who received TURBT were enrolled in the analysis, and their baseline characteristics were similar. During the TURBT, 24 (15.8%) obturator nerve reflexes and 9 (5.9%) bladder perforations occurred, while none happened during the TmLRBT. After surgery, TmLRBT patients had fewer postoperative gross hematuria (38.1 vs. 96.7%, p < 0.001) and postoperative irrigation (27.6 vs. 92.7%, p < 0.001), and its irrigation duration was significantly shorter (2.3 vs. 3.3 day, p < 0.001). During the follow-up, no significant difference in the recurrence rate was detected (p = 0.315). Conclusions: TmLRBT is a safer technique than conventional TURBT in the treatment of NMIBC, and it could offer better specimens for pathologic assessment while the cancer control was not compromised.
Straight to the Point: What Do We Know So Far on Hair Straightening?
Authors: Barreto Taynara , Weffort Flavia , Frattini Simone , Pinto Giselle , Damasco Patricia , Melo Daniel
Published: March 2021

Background: Hair represents a valued aspect of human individuality. The possibility of having an easy to handle hairstyle and changing it from time to time promoted an increasing search for chemical hair transformations, including hair straightening. Hair straightening is the process used to convert curly into straight hair. Aims: This review aims to discuss hair straightening, addressing techniques, products, methods of application, consequences to hair shafts, recommendations on this topic, and the risks involving the safety of both the user and the performing professional. Methods and Results: The terms “straightening” AND “hair,” “straightening” AND “alopecia,” and “straightening” AND “human hair” were used to perform a literature search in MEDLINE through PubMed until July 15, 2020. We limited the search to articles available in English, considering those mentioning alternatives to straighten the hair. We had a total of 33 relevant articles. Conclusions: This article will help dermatologists to advise their patients, providing a more suitable orientation on how to get the best outcome without risking one’s safety.
Learning Curve of an Innovative “3-Port” Laparoscopic Radical Prostatectomy: A Single-Center Analysis from 2016 to 2019
Authors: Xu Ben , Ma Bing-lei , Peng Yi-ji , Zhang Qian
Published: March 2021

Background: “Three-port” laparoscopic radical prostatectomy (LRP) has been applied as a substitution for the conventional 4- to 5-port LRP to treat prostate cancer (PCa) patients in our institution. Objective: To evaluate the learning curve of an innovative “3-port” LRP for PCa patients. Methods: 206 patients who received “3-port” LRP were retrospectively reviewed between January 2016 and December 2019 at our institution. According to the different years of operations performed, all of the patients were divided into group A (No. 1–50), group B (No. 51–107), group C (No. 108–160), and group D (No. 161–206). A learning curve was depicted by analyzing the parameters of operative time (OT), estimated blood loss (EBL), hospitalization, and drainage indwelling days. Results: All groups were comparable with regard to the preoperative characteristics (p > 0.05). The sloping learning curve for the surgeon showed that OT and EBL were strongly correlated with an accumulated experience when compared between group A and the other groups (p < 0.05), denoting that the surgical skill of the “3-port” LRP can be fully mastered after around 50 cases. Although no significant correlation with additional experience was observed in the hospitalization and drainage indwelling days among groups, a tendency towards less hospitalization and drainage indwelling days was still reflected. Conclusions: Our 4-year analysis based on a single-center experience exhibits that the innovative “3-port” LRP appears to be favorable with decreasing tendency in OT and EBL with experience accumulation. In view of its advantage of perioperative parameters with an evidently improved learning curve, it should be recommended in the clinical practice!
Role of Metabolic Risk Factors, Family History, and Genetic Polymorphisms (PPARγ and TCF7L2) on Type 2 Diabetes Mellitus Risk in an Asian Indian Population
Authors: Chaudhuri Plaban , Das Mithun , Lodh Indrani , Goswami Riddhi
Published: March 2021

Introduction: Women with family history of diabetes (FHD) are at significantly increased risk of developing gestational diabetes mellitus which may eventually lead to type 2 diabetes mellitus (T2DM) in later life. Objective: This study investigates the role of FHD on metabolic markers and gene polymorphisms and hence on T2DM susceptibility in nondiabetic pregnant women and the subsequent risks in their newborns. Materials and Methods: The present study was conducted on 200 healthy (nondiabetic and normotensive) adult Asian Indian women, including 100 with and 100 without FHD, living in and around Kolkata, India. During the gestational period, they were studied twice and followed up till delivery. During delivery, both mothers’ venous blood and cord blood were collected to estimate serum CRP, glucose, and lipid profiles of the respective mothers and their newborns. Genotyping of PPARγ and TCF7L2 polymorphisms was done from these blood samples. Results: A comparison of the metabolic variables among the subjects with and without FHD revealed significant differences among them. We also found close relationship between mothers and their newborn babies in terms of both PPARγ (rs1801282) C/G and TCF7L2 (rs7903146) C/T polymorphisms. More specifically, genotyping results for mothers with FHD and their newborn babies showed high concordance in inheritance of alleles: (i) for PPARγ via the risk allele G (74.0%) which is carried over to the newborn babies (64.5%) and (ii) for TCF7L2 via the risk allele T (73.0%) which is carried over to the newborn babies (68.5%). Conclusion: This study leads to the conclusion that Asian Indian women population based in Kolkata, India, are ethnically and genetically predisposed to the risk factors of diabetes through FHD, which is reflected in their gestational phase, and it has a significant implication on their birth outcomes.
Clinical Outcome of Acute Ischemic Strokes in Patients with COVID-19
Authors: Calmettes Julie , Peres Roxane , Goncalves Bruno , Varlan David , Turc Guillaume , Obadia Michael , Nardin Clotilde , Meppiel Elodie , De Broucker Thomas , Mazighi Mikael , Lyoubi Aicha
Published: March 2021

Introduction: Acute ischemic stroke (AIS) and thrombotic events (TEs) were reported in patients with COVID-19. Clinical outcome of AIS in the course of COVID-19 remains unknown. We compared early clinical outcome and mortality of COVID-positive (+) patients admitted for AIS with COVID-negative (−) ones. We hypothesized that COVID+ patients would have poorer clinical outcomes and present a higher rate of TEs and mortality compared with COVID− ones. Methods: In this multicentric observational retrospective study, we enrolled patients over 18 years old admitted for AIS in 3 stroke units of the Parisian region during lockdown from March 17, 2020, to May 2, 2020. COVID-19 status as well as demographic, clinical, biological, and imaging data was collected retrospectively from medical records. Poor outcome was defined as modified Rankin score (mRS) 3–6 (3–6) at discharge. We also compared TE frequency and mortality rate through a composite criterion in both groups. Results: Two hundred and sixteen patients were enrolled; mean age was 68 years old, and 63% were male. Forty patients were CO­VID+ (18.5%) and 176 were COVID−. Obesity was statistically more frequent in the COVID+ group (36 vs. 13% p < 0.01). The percentage of patients with mRS (3–6) at discharge was higher in the COVID+ group compared with the COVID− group (60 vs. 41%, p = 0.034). The main predictor of presenting a mRS (3–6) at discharge was high NIHSS score at admission (OR, CI 95%: 1.325, 1.22–1.43). Mortality rate was higher in the COVID+ group (12 vs. 3.4%, p = 0.033) as well as TE frequency (15 vs. 2.8%, p < 0.01). Conclusion: In this study, patients with AIS infected by SARS-CoV-2 showed a poorer early outcome than COVID− ones. However, when compared to other factors, COVID-19 was not a significant predictor of poor outcome. Vascular morbidity and mortality rates were significantly higher in the COVID+ group compared with the COVID− group.
Augmented Reality with HoloLens® in Parotid Tumor Surgery: A Prospective Feasibility Study
Authors: Scherl Claudia , Stratemeier Johanna , Rotter Nicole , Hesser Jürgen , Schönberg Stefan O. , Servais Jérôme J. , Männle David , Lammert Anne
Published: March 2021

Introduction: Augmented reality can improve planning and execution of surgical procedures. Head-mounted devices such as the HoloLens® (Microsoft, Redmond, WA, USA) are particularly suitable to achieve these aims because they are controlled by hand gestures and enable contactless handling in a sterile environment. Objectives: So far, these systems have not yet found their way into the operating room for surgery of the parotid gland. This study explored the feasibility and accuracy of augmented reality-assisted parotid surgery. Methods: 2D MRI holographic images were created, and 3D holograms were reconstructed from MRI DICOM files and made visible via the HoloLens. 2D MRI slices were scrolled through, 3D images were rotated, and 3D structures were shown and hidden only using hand gestures. The 3D model and the patient were aligned manually. Results: The use of augmented reality with the HoloLens in parotic surgery was feasible. Gestures were recognized correctly. Mean accuracy of superimposition of the holographic model and patient’s anatomy was 1.3 cm. Highly significant differences were seen in position error of registration between central and peripheral structures (p = 0.0059), with a least deviation of 10.9 mm (centrally) and highest deviation for the peripheral parts (19.6-mm deviation). Conclusion: This pilot study offers a first proof of concept of the clinical feasibility of the HoloLens for parotid tumor surgery. Workflow is not affected, but additional information is provided. The surgical performance could become safer through the navigation-like application of reality-fused 3D holograms, and it improves ergonomics without compromising sterility. Superimposition of the 3D holograms with the surgical field was possible, but further invention is necessary to improve the accuracy.
A Rare Case: Primary Venous Malformation in Parietal Bone
Authors: Yarar Serhat , Uyar Ilker , Yildirim Mehmet Emin Cem , Dadacı Mehmet , Ince Bilsev
Published: March 2021

Primary intraosseous vascular malformations (PIVMs) are rare intraosseous lesions, accounting for approximately 0.5–1% of all intraosseous tumours. In this case report, we aimed to present a rare case of intraosseous vascular malformation causing a large lytic area in the parietal bone. A 25-year-old male patient was admitted to the clinic with a mass on the parietal bone. On physical examination, it was observed that the hair density on the mass was decreased, the mass had a soft consistency, and there was no pain on palpation. The patient was operated under local anaesthesia with a provisional diagnosis of a trichilemmal cyst. However, intraoperative diagnosis was a vascular malformation. There was a 3-cm full-thickness defect on the parietal bone caused by the lesion. The mass was excised completely while preserving the integrity of the dura. The resulting defect was reconstructed with bilateral rotation advancement flaps. The calvarial defect was not reconstructed due to equipment inadequacy. No complications were encountered in the postoperative period. Ninety-three PIVM cases have been reported in the skull since 1845. In very few of these cases, the mass is located in the parietal bone. The pathogenesis of PIVMs is not completely understood. The definitive diagnosis is made by histopathological examination. The therapeutic gold standard is surgery. Surgeons should keep in mind that radiological examination before the operation could prevent undesirable complications.
Evaluation of Sequential Urine Analysis when Selecting Candidates for Vesicoamniotic Shunting in Lower Urinary Tract Obstruction
Authors: Koch Antoine , Favre Romain , Weingertner Anne-Sophie , Zaloszyc Ariane , Kohler Monique , Guerra Fernando , Rosenblatt Jonathan , Muller Françoise , Dreux Sophie , Sananès Nicolas
Published: March 2021

Objective: The objective of our study was to assess the utility of sequential fetal urine analysis in severe lower urinary tract obstruction (LUTO) when selecting cases suitable for vesicoamniotic shunting. Material and Methods: This was a retrospective cohort study of cases of severe LUTO treated in our fetal medicine center from 1994 to 2013. Two fetal bladder samples were taken 24–48 h apart to assess renal function. A vesicoamniotic shunt was inserted in case of improvement in urinary biochemistry between the 2 samples. We assessed perinatal morbidity and mortality and renal function at 5 years. Results: Among a total of 26 LUTO cases with sequential urine analysis, 5 showed normal urinary biochemistry, 13 were abnormal, and 8 improved between the 2 samples. These 8 cases underwent vesicoamniotic shunt placement, leading to the birth of 6/8 (75%) live infants, 5/6 (83%) of whom had normal renal function at 5 years. The 5 cases with normal biochemistry occasioned 2 neonatal deaths and 3 children with normal renal function at 5 years. Elective termination of pregnancy was requested by parents for the fetuses exhibiting abnormal biochemistry. Conclusion: An improvement in urinary biochemistry between 2 sequential fetal bladder punctures in severe LUTO could be an effective criterion in the selection of candidates for vesicoamniotic shunting. However, the benefit of a shunt in fetuses with normal amniotic fluid remains to be evaluated in clinical trials.
Preoperative Cervical Length Predicts the Risk of Delivery within One Week after Pleuroamniotic Shunt in Fetuses with Severe Hydrothorax
Authors: Gámez-Varela Alma , Martínez-Rodríguez Miguel , López-Briones Hugo , Luna-García Jonahtan , Chávez-González Eréndira , Villalobos-Gómez Rosa , Hernandez-Andrade Edgar , Cruz-Martínez Rogelio
Published: March 2021

Objective: The objective of this study was to assess the predictive performance of preoperative cervical length (CL) for delivery within 1 week after pleuroamniotic shunting (PAS) in fetuses with severe hydrothorax. Methods: A prospective cohort of fetuses with severe hydrothorax referred to our fetal surgery center in Querétaro, Mexico from January 2012 to July 2020. Severe fetal hydrothorax was diagnosed as an accumulation of fluid within the fetal pleural space accompanied with severe bilateral lung compression, mediastinal shift, polyhydramnios, and/or hydrops. Transvaginal CL was measured immediately before PAS, and a short cervix was defined as that <25 mm. The interval from fetal intervention to delivery, prevalence of preterm prelabor rupture of membranes (PPROMs), and associations with delivery within the first week after PAS according to a short or a normal CL, were evaluated. Results: Thirty-five pregnancies with severe fetal hydrothorax treated with PAS were evaluated. Median gestational age at PAS was (weeks + days) 31+2 (range, 26+0–36+1). Two (5.7%) and 7 (20.0%) cases delivered within the first 24 h and 1 week after PAS, respectively. Ten (28.6%) women had a short cervix before PAS, while 25 (71.4%) had normal preoperative CL. Women with a short cervix showed lower mean interval between fetal intervention and delivery (2.4 vs. 5.5 weeks, p = 0.01), and higher prevalence of PPROM (50 vs. 12%, p = 0.01), as compared to women with a nonshort cervix. Preoperative short cervix was associated with significantly higher risk of delivery within the first 24 h (20.0 vs. 0%, respectively, p < 0.05) and 1 week after PAS (50.0 vs. 8.0%, respectively, p < 0.01) compared with pregnancies with normal preoperative CL. Conclusion: In pregnancies with severe fetal hydrothorax candidates for pleuroamniotic shunt, identification of a short cervix before fetal intervention can predict delivery within 1 week after the surgical procedure.
Successful Treatment of Coexistent Acne Fulminans and Severe Hidradenitis Suppurativa with Adalimumab
Authors: Kontochristopoulos George , Agiasofitou Efthymia , Platsidaki Eftychia , Kapsiocha Anastasia , Gregoriou Stamatios , Rigopoulos Dimitrios
Published: March 2021

The coexistence of hidradenitis suppurativa (HS) and acne fulminans (AF) has only recently been reported in the literature. We present a case of a 17-year-old man who presented with a 2 years history of severe acne and HS. He was initially started on oral clindamycin and rifampicin for 3 months with no clinical improvement. Acne lesions became worse with the presence of nodules and necrotic ulcers, while weight loss, low-grade fever, back and knee pain, and psychological distress were noted. We prescribed adalimumab in its standard dosing regimen. Remission of AF was achieved in 3 months, whereas adalimumab has not been as effective in treating the HS lesions. Its dosage was increased to 80 mg weekly and more than 80% clinical improvement of HS lesions was obtained in 2 months. The patient maintained on this dosage till this day and efficacy is sustained. TNF-α inhibitors are considered an effective option in the treatment of HS, while it has been also suggested as a treatment option in AF. Our patient was successfully treated with adalimumab. Since the coexistence of HS and AF has a devastating emotional effect on the patient, there is an urgent need to implement therapeutic approaches.
A Predictive Score of Antitumour Activity of Novel Agents in Cancer Patients Treated in Early Phase Studies
Authors: Liu Runhan , Gomes Ana , Ao Geriletu , de Miguel Maria , Boni Valentina , Moreno Irene , Cardenas Rebollo Jose Miguel , Ugidos Lisardo , Calvo Emiliano
Published: March 2021

Introduction: Phase I trials aim to determine the maximum-tolerated dose of a particular drug while minimizing the number of patients exposed to either sub-therapeutic doses or severe toxicity. Thus, patient selection for phase I trials is a key component of any clinical trial design. Though several studies have been made to address this issue, patient selection still represents a major clinical challenge that needs further investigation. Methods: Twenty-nine baseline clinical and analytical characteristics of 773 consecutive patients treated in phase I trials between 2008 and 2016 in START Madrid-CIOCC were analysed and correlated to objective response (OR), progression-free survival, median overall survival, toxicity, and treatment type. The ones associated to OR in the univariate analysis were included in the stepwise logistic regression multivariate and Cox analysis. The statistically significant ones were included in a predictive score (named here as the Madrid score) of antitumour activity. Results: Body mass index (BMI) >25 (p = 0.027), two or less previous lines of treatment (p = 0.007), and normal levels of alkaline phosphatase (ALP) (p = 0.007) were found to positively correlate to radiological response. A Madrid score was generated using these three factors as predictive parameters: compared to a score of 2–3 (where 2 or 3 of these variables are altered), a score of 0–1 is associated with longer survival time (11.6 vs. 8.6 months; p = 0.005) and overall response (17 vs. 7.6%; p = 0.003). Conclusion: The predictive Madrid score, based on the BMI, number of prior lines of treatment, and ALP levels, might be helpful to accurately select patients who would benefit from oncology phase I clinical trials.
Glabellare Falten: Wie die Wirkung von Botulinumtoxin A verlängert werden kann
Authors: Prager Welf
Published: March 2021

Background: Recently reported clinical data provides evidence that increasing the dose of botulinum toxin A increases the duration of efficacy. A 2-stage Phase 2, randomized, double-blind study investigated the duration of effect and safety of IncobotulinumtoxinA (INCO; Xeomin®, Bocouture®; Merz Pharmaceuticals GmbH, Frankfurt am Main, Germany) at doses higher than the approved 20 units (U) for glabellar frown lines (GFL). Primary safety and efficacy endpoints of Stage 1 are reported here. Methods: 151 subjects with moderate-to-severe GFL were randomized 1:2:2 to receive a single treatment with 20U, 50U, or 75U INCO. The primary efficacy endpoint was median duration of at least 1-point improvement from baseline as assessed by investigator at maximum frown on the Facial Wrinkle Scale. Results: The median duration of effect was 185 days for the 50U dose group (95% CI: [182, 205]) and 210 days for the 75U dose group (95% CI: [182, 217]). Duration of effect was significantly longer for 75U vs 50U (P = 0.0400) and 20U (P = 0.0166) despite the study not being powered for confirmatory statistical significance testing between the dose groups. Duration of effect was also longer for 50U vs 20U, however; statistical significance was not reached (P = 0.4349). The incidence of treatment-related adverse events was low across all doses (20U:2 [6.7%], 50U:6 [10.0%] and 75U:8 [13.1%]). Conclusions: These results demonstrate a dose effect of at least 6 months duration with higher doses in the majority of GFL subjects. All doses were well tolerated and safety was consistent with the known safety profile of 20U INCO for GFL. J Drugs Dermatol. 2020;19(10):985–991. doi:10.36849/JDD.2020.5454
A Model based Approach for Evaluating the Reliability of the Services in the Service-oriented Architecture
Authors: Alipour Behzad , Abadi Ali Haroon
Published: March 2021

Service-oriented architecture presents a frame in which the system functions are defined as a series of the distributed services in the intended sizes of the organization. These services are called by the other software and also are used for building the new services. Although this architecture offers a simple solution for building the distributed systems with loosely coupling, it introduces some additional concerns. One of the main concerns in designing a SOA system is general reliability of the system. Then the new technique for modeling the reliability is needed for certificating the services. Regarding to this weakness, in this paper, a certification method for the reliability in which services have been simulated as the discrete Markov chains, this work presents a model for estimating the reliability by exploiting the mean and variance of the visits obtained from analyzing Markov chain and integrating them into the reliability of the characteristics of each individual service. Results show that in the proposed method, less fault-tolerance than the recent methods for predicting the reliability of the systems is used.
Livestock Pedigree Data Management Using Radio Frequency Identification
Authors: Widyantara Helmy , Harianto Harianto , Wibowo Madha Christian , Mardiana Rai , Rasmana Susijanto T.
Published: March 2021

Boerka goat is a crossbreeding product of Australian boer goat and Indonesian local kacang goat. Boerka goat produce meat better than kacang goat and more suited to Indonesian climate than boer goat. In order to develop an optimal boerka population, the crossbreeding process beetwen the next generation has to observed very carefully. To support that purpose, the things needed are registration system for newborn livestock and data management system of pedigree of livestock. It could help the breeder to find a perfect seed for their goat. The newborn goatling will fitted with an RFID integrated electronic ear-tag. This unique ID number will be sent to an online database server together with the neccessary datas of the baby goat. These datas will online managed using website that operated by the breeders. In addition to livestock datas, the website also provides information about the goat farm, the owner, and also the migration or transaction of the livestocks from one to another farm or to the outside goat farm community.
Christ and His Representation, One or Two? The Image Theologies of Theodore of Stoudios, Leo of Chalcedon and Eustratius of Nicaea
Authors: Krausmüller Dirk
Published: March 2021

This article discusses the image theologies of Theodore of Stoudios, Leo of Chalcedon and Eustratius of Nicaea. It focuses on two topics: the relation between archetype and image and the identity of hypostasis. It is argued that Theodore’s image theology was contradictory, and that Leo of Chalcedon and Eustratius of Nicaea each developed one aspect of Theodore’s argumentation while neglecting the other.
Geneses and Aftereffects: The Subtleties of a Coup d’État in Zimbabwe and Their Post-coup Consequences
Authors: Dodo Obediah
Published: March 2021

In 2017, Zimbabwe recorded a military intervention that left President Mugabe out of office. The replacement government has created a raft of controversial measures and policies. The study therefore explored the implications of the coup to policy formulation and execution vis-à-vis the rights and security of the people. The study followed a democratic governance framework. It focused on demonstration participants and active soldiers during the coup. Twenty civilian demonstrators and ten soldiers were sampled from Harare which was the centre of the coup. Data were analysed using Narrative Latent Content method. The study established that policy formulation is driven by both emotions and the desire to protect committers of the coup from possible accountability. It also established that in-order to safeguard its interests, the regime has crafted repressive laws that are however unsustainable.
Sufi-Vedāntic Interactions and Literary Interconnections in the Gulzār-i ḥāl by Banwālīdās
Authors: Cappello Giuseppe
Published: March 2021

This paper focuses on the Gulzār-i ḥāl by Banwālīdās (1662–3), a Persian adaptation of the Sanskrit allegorical drama Prabodhacandrodaya composed by Kṛṣṇamiśra (not long after 1065). It is also hypothesised that Banwālīdās may have used a Braj Bhāṣā version of the same text – by the poet Nanddās entitled Prabodhacandrodaya Nāṭaka (c. 1570) –, as intermediary with the original Sanskrit. Regardless of the source that our author used to realise his Gulzār-i ḥāl, the filter used to adapt Advaitic elements to the Islamic mystical context was the Waḥdat al-Wujūd (“Unity of Being”), or the tradition of mysticism that was heavily inspiring Sufi traditions of South Asia at that time. Moreover, a codicological analysis of the Gulzār-i ḥāl’s manuscript tradition has brought to light that both Hindu and Muslim readership received the text. In this paper, I will show that the interpretative engagement of Banwālīdās carried on a tradition of philosophical studies that did not consider Sufi and Vedāntic metaphysics as separated entities but as elements that – in dialogue with each other – searched for a common answer to the ultimate truth.
Darwin wasps of the subfamily Pimplinae (Hymenoptera: Ichneumonidae) of Mexico: genera Neotheronia Krieger, Nomosphecia Gupta and Xanthopimpla Saussure
Authors: KHALAIM ANDREY I. , RUÍZ-CANCINO ENRIQUE
Published: March 2021

Mexican species of three pimpline genera, Neotheronia Krieger (24 species), Nomosphecia Gupta (two species) and Xanthopimpla Saussure (one species) are reviewed. Five species of Neotheronia are described as new to science: N. altacima sp. nov., N. bonita sp. nov., N. juanitae sp. nov., N. tequila sp. nov. and N. zaldivari sp. nov. Neotheronia septemtrionalis Krieger, 1905 is found to be a junior synonym of N. nigrolineata (Brullé, 1846) (syn. nov.). Seven species of Neotheronia are new records from Mexico: N. bostrandae Gauld, N. charli Gauld, N. donovani Gauld, N. hespenheidei Gauld, N. lizzae Gauld, N. lloydi Gauld and N. matamorosi (Brullé). Moreover, Neotheronia concolor Krieger, N. lineata (Fabricius), N. mellosa (Cresson) and N. nigrolineata (Brullé) are recorded for the first time from Honduras, and N. rosai Gauld is recorder for the first time from Guatemala. South American species Neotheronia cristata Krieger is excluded from the Mexican fauna. Identification keys to species of Neotheronia and Nomosphecia occurring in Mexico are provided.
Redescription of Raggophyllum Nickle, 1967 (Orthoptera: Tettigoniidae: Phaneropterinae) with description of a new species from Brazilian Amazon Rainforest and placement in Microcentrini Brunner von Wattenwyl, 1878
Authors: DE MELLO MENDES DIEGO MATHEUS , RAFAEL JOSÉ ALBERTINO
Published: March 2021

Raggophyllum Nickle, 1967 is a monotypic genus, including Raggophylluym spinosum, and recorded in Peru and Bolivia. In this work, Raggophyllum is redescribed and assigned to the Microcentrini, based on the type species Raggophylluym spinosum. Raggophyllum rubrofemoratum sp. nov. in described from Brazil, Acre and Amazonas, and it is the first record for the genus in Brazil. The male genitalia and the stridulatory file morphology are described for the first time. A distribution map, notes on the habitat, and commentaries on their distribution among Amazonian endemism areas are included.
Role of the climatological intertropical convergence zone in the seasonal footprinting mechanism of the El Niño-Southern Oscillation
Authors: Park Jae-Heung , Sung Mi-Kyung , Yang Young-Min , Zhao Jiuwei , An Soon-Il , Kug Jong-Seong
Published: March 2021

The North Pacific Oscillation (NPO), a primary atmospheric mode over the North Pacific in boreal winter, is known to trigger the El Niño-Southern Oscillation (ENSO) in the following winter, the process of which is recognized as the seasonal footprinting mechanism (SFM). Based on the analysis of model simulations from the Coupled Model Intercomparison Project Phase 5 (CMIP5), we found that the SFM acts differently among models, and the correlation between the NPO and subsequent ENSO events, called the SFM efficiency, depends on the background mean state of the model. That is, SFM efficiency becomes stronger as the climatological position of the Pacific Intertropical Convergence Zone (ITCZ) moves poleward, representing an intensification of the northern branch of the ITCZ. When the Pacific ITCZ is located poleward, the wind-evaporation-sea surface temperature (SST) feedback becomes stronger as the precipitation response to the SST anomaly is stronger in higher latitudes compared to that of lower latitudes. In addition, such active ocean-atmosphere interactions enhance NPO variability, favoring the SFM to operate efficiently and trigger an ENSO event. Consistent with the model results, the observed SFM efficiency increased during the decades in which the northern branch of the climatological ITCZ was intensified, supporting the importance of the tropical mean state of precipitation around the Pacific ITCZ.
Cross-validation of active and passive microwave snowfall products over the continental United States
Authors: Mroz Kamil , Montopoli Mario , Battaglia Alessandro , Panegrossi Giulia , Kirstetter Pierre , Baldini Luca
Published: March 2021

Surface snowfall rate estimates from the Global Precipitation Measurement (GPM) mission’s Core Observatory sensors and the CloudSat radar are compared to those from the Multi-Radar Multi-Sensor (MRMS) radar composite product over the continental United States during the period from November 2014 to September 2020. The analysis includes: the Dual-Frequency Precipitation Radar (DPR) retrieval and its single frequency counterparts, the GPM Combined Radar Radiometer Algorithm (CORRA), the CloudSat Snow Profile product (2C-SNOW-PROFILE) and two passive microwave retrievals, i.e., the Goddard PROFiling algorithm (GPROF) and the Snow retrievaL ALgorithm fOr gMi (SLALOM). The 2C-SNOW retrieval has the highest Heidke Skill Score (HSS) for detecting snowfall among the products analysed. SLALOM ranks second; it outperforms GPROF and the other GPM algorithms, all detecting only 30% of the snow events. Since SLALOM is trained with 2C-SNOW, it suggests that the optimal use of the information content in the GMI observations critically depends on the precipitation training dataset. All the retrievals underestimate snowfall rates by a factor of two compared to MRMS. Large discrepancies (RMSE of 0.7 to 1.5 mm h-1) between space-borne and ground-based snowfall rate estimates are attributed to the complexity of the ice scattering properties and to the limitations of the remote sensing systems: the DPR instrument has low sensitivity, while the radiometric measurements are affected by the confounding effects of the background surface emissivity and of the emission of supercooled liquid droplet layers.
Indocyanine Green Fluorescence Angiography of the Transverse Cervical Arterial Supply to Clavicle Flaps: An Anatomical Study
Authors: Muangsiri Pichtat , Tanjapatkul Rungkit , Sriswadpong Papat , Jomkoh Pojanan , Jirawatnotai Supasid
Published: March 2021

Objective

To describe the anatomy of the transverse cervical artery and to prove its perfusion to the clavicle using indocyanine green fluorescence angiography as an alternative vascularized bone for head and neck reconstruction.

Study Design

Cadaveric dissection.

Setting

Anatomy lab.

Methods

Twenty‐two necks and shoulders from 11 fresh‐frozen cadavers were dissected. The transverse cervical artery diameter, length, emerging point, and the length of clavicle segment harvested were described. Photographic and near‐infrared video recordings of the bone’s medial and longitudinal cut surfaces were taken prior to, during, and after indocyanine green injection.

Results

The transverse cervical artery originated from the thyrocervical trunk and emerged at the level of the medial one‐third of the clavicle in 22 of 22 (100%) specimens. The average length of the pedicle was 3.6 cm (range, 2.2‐4.4 cm), and the mean diameter was 2.5 mm (range, 1.8‐3.4 mm). The harvested bone had a mean length of 5.1 cm (range, 4.3‐5.8 cm). After injecting the indocyanine green, 22 of 22 (100%) specimens showed enhancement in the periosteum, bony cortex, and medulla.

Conclusion

The middle third of the clavicle can be reliably harvested as a vascularized bone with its perfusion solely from the transverse cervical artery pedicle, as shown by the near‐infrared fluorescence imaging. The pedicle was sizable and constant in origin.