bluuebunny/crossref_metadata_2025 huggingface dataset:
Healthcare provider and drug dispenser knowledge and adherence to guidelines for the case management of malaria in pregnancy in the context of multiple first-line artemisinin-based combination therapy in western Kenya
Authors: Osoro Caroline B. , Dellicour Stephanie , Ochodo Eleanor , Young Taryn , ter Kuile Feiko , Gutman Julie R. , Hill Jenny
Published: September 2023

Background

Concerns about emerging resistance to artemether-lumefantrine (AL) in Africa prompted the pilot introduction of multiple first-line therapies (MFT) in Western Kenya, potentially exposing women-of-childbearing-age (WOCBA) to anti-malarials with unknown safety profiles in the first trimester. The study assessed healthcare provider knowledge and adherence to national guidelines for managing malaria in pregnancy in the context of the MFT pilot.

Methods

From March to April 2022, a cross-sectional study was conducted in 50 health facilities (HF) and 40 drug outlets (DO) using structured questionnaires to assess pregnancy detection, malaria diagnosis, and treatment choices by trimester. Differences between HF and DO providers and between MFT and non-MFT HFs were assessed using Chi-square tests.

Results

Of 174 providers (77% HF, 23% DO), 56% were from MFT pilot facilities. Most providers had tertiary education; 5% HF and 20% DO had only primary or secondary education. More HF than DO providers had knowledge of malaria treatment guidelines (62% vs. 40%, p = 0.023), received training in malaria in pregnancy (49% vs. 20%, p = 0.002), and reported assessing for pregnancy in WOCBA (98% vs. 78%, p < 0.001). Most providers insisted on parasitological diagnosis, with 59% HF using microscopy and 85% DO using rapid diagnostic tests. More HF than DO providers could correctly name the drugs for treating uncomplicated malaria in the first trimester (oral quinine, or AL if quinine is unavailable) (90% vs. 58%, p < 0.001), second and third trimesters (artemisinin-based combination therapy) (84% vs. 70%, p = 0.07), and for severe malaria (parenteral artesunate/artemether) (94% vs. 60%, p < 0.001). Among HF providers, those in the MFT pilot had more knowledge of malaria treatment guidelines (67% vs. 49%, p = 0.08) and had received training on treatment of malaria in pregnancy (56% vs. 32%, p = 0.03). Few providers (10% HF and 12% DO) had adequate knowledge of malaria treatment in pregnancy, defined as the correct drug and dose for uncomplicated and severe malaria in all trimesters.

Conclusions

Knowledge of national malaria in pregnancy treatment guidelines among providers in Western Kenya is suboptimal. Robust training on appropriate anti-malarial and dosage is needed, particularly given the recent change in recommendation for artemether-lumefantrine use in the first trimester. Supervision of DO and HF practices is essential for correct treatment of malaria in pregnancy in the context of MFT programmes.
CD39 and LDHA affects the prognostic role of NLR in metastatic melanoma patients treated with immunotherapy
Authors: Mallardo Domenico , Fordellone Mario , White Andrew , Ottaviano Margaret , Sparano Francesca , Bailey Michael , Facchini Arianna Bianca , Ong Sufey , Maiolino Piera , Caracò Corrado , Church Sarah , Cavalcanti Ernesta , Warren Sarah , Budillon Alfredo , Cesano Alessandra , Simeone Ester , Chiodini Paolo , Ascierto Paolo Antonio
Published: September 2023

Background

Identifying response markers is highly needed to guide the treatment strategy in patients with metastatic melanoma.

Methods

A retrospective study was carried out in patients with unresectable/metastatic melanoma (stage IIIb–IV), treated with anti-PD-1 in the first line setting, to better explore the role and the timing of neutrophil/lymphocyte ratio (NLR) as potential biomarker of response. The relationship of NLR with inflammation-immune mediators and the underlying negative effect of raising NLR during immunotherapy, have been investigated with transcriptomic gene analysis.

Results

The results confirmed previous findings that a high baseline NLR is associated with a poorer prognosis and with higher serum level of lactate dehydrogenase (LDH), regardless of the presence of brain metastases. The transcriptomic analysis showed that high baseline NLR is associated with a characteristic gene signature CCNA1, LDHA and IL18R1, which correlates with inflammation and tumorigenesis. Conversely, low baseline NLR is associated with the signature CD3, SH2D1A, ZAP70 and CD45RA, linked to the immune-activation. The genes positively associated with NLR (CD39 (ENTPD1), PTEN, MYD88, MMP9 and LDH) are involved in processes of immunosuppression, inflammation and tumor-promoting activity. Increased expression of CD39 correlated with TGFβ2, a marker of the N2 neutrophils with immunosuppressive activity.

Conclusions

These results suggest that increasing NLR is associated with an increased neutrophil population, with polarization to the N2 phenotype, and this process may be the basis for the negatively prognostic role of NLR.
Clinical characteristics of abruptly increased paediatric patients with Omicron BF.7 or BA.5.2 in Beijing
Authors: Yu Lei , Wang Congying , Li Xiaoyun , Wang Xinning , Kang Yingying , Ma Xiaomei , Sun Rui , Sun Yu , Zhu Runan , Jia Liping , Yao Yao , Li Xiaohui , Zhang Daitao , Pan Yang , Lv Bing , Yuan Jing , Zhao Linqing , Gu Qinglong , Zhang Jian
Published: September 2023

Background

The coronavirus disease 2019 outbreak has hit Beijing since mid-Nov, 2022, with soaring growth of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among children. Therefore, it is vital to determine the clinical manifestations of epidemic SARS-CoV-2 strains in paediatric patients.

Methods

In this study, nucleic acid tests (NATs) for SARS-CoV-2 were performed in paediatric outpatients with symptoms of acute respiratory tract infection during 18 Nov–6 Dec, 2022. Half of the outpatients positive for SARS-CoV-2 were randomly selected to screen for other respiratory pathogens, whereas those with low cycle threshold values in SARS-CoV-2 NATs were amplified and sequenced to determine the SARS-CoV-2 variants. Finally, children positive for SARS-CoV-2 with clinical information in detail were enrolled in a follow-up study to identify potential factors significantly associated with long recovery.

Results

Among 9625 paediatric outpatients tested for nucleic acid of SARS-CoV-2, 733 (7.62%, 733/9625) were identified as SARS-CoV-2 NAT positive, with only three (0.82%, 3/366) co-infected with other pathogens among 366 randomly selected patients, and 71 (62.83%) determined as Omicron subvariant BF.7 and 42 (37.22%) as BA.5.2 among 113 successfully sequenced. Among the 681 patients with complete clinical information, fever was the most common symptom (96.8%). In a follow-up study of 592 patients, 46.96% became asymptomatic on the third day and 65.71% on the fifth day. Only 1.7% of infected children experienced febrile seizures. Combined with abnormal C-reactive protein, a higher percentage of antibiotics administration was observed. More co-living members and longer duration of first symptoms served as independent risk factors for long-term recovery, especially in children vaccinated for SARS-CoV-2.

Conclusions

BF.7 and BA.5.2 were the dominate Omicron subvariants and caused milder infections during the SARS-CoV-2 outbreak in Beijing. The number of co-living members and duration of first symptoms were independent risk factors for long-term recovery.
Cognition of abdominal pain and abdominal discomfort in Chinese patients with irritable bowel syndrome with diarrhea
Authors: Lu Jia , Chen Yang , Shi Lili , Li Xiaoqing , Fei Guijun , Li Ji , Yang Aiming , Fang Xiucai
Published: September 2023

Background

In Asia, the proportion of patients with irritable bowel syndrome (IBS) with abdominal discomfort alone is significantly higher than that in western countries. The purposes of this study are to understand the cognition of abdominal pain and abdominal discomfort in Chinese patients with IBS and to compare the clinical characteristics of patients with abdominal pain alone and with abdominal discomfort alone.

Methods

Patients with IBS with diarrhea (IBS-D) who met the Rome III diagnostic criteria and had episodes of at least one day/week were consecutively enrolled. The cognition of abdominal pain and abdominal discomfort were investigated through face-to-face unstructured interview. Patients were divided into a pain group and a discomfort group according to the cognition interviews, then the characteristics and severity of symptoms (IBS symptom severity scale, IBS-SSS), IBS quality of life (IBS-QOL) and psychological state were compared between groups.

Results

A total of 88 patients with IBS-D were enrolled. Most of the patients with self-reported abdominal pain described their pain as spasm/cramping; patients with self-reported abdominal discomfort had as many as 24 different descriptions of discomfort. Most patients having abdominal pain and discomfort could accurately distinguish the two symptoms. The degree of abdominal pain in the pain group was higher than abdominal discomfort in the discomfort group (P = 0.002). There was no significant difference in IBS-SSS, extra-intestinal pain, IBS-QOL, and psychological state between the two groups.

Conclusions

For Chinese patients with IBS-D, abdominal pain and abdominal discomfort are two different symptoms, but they have similar clinical features.

Trial registration

ChiCTR, ChiCTR1900028082. Registered 11 December 2019 - Retrospectively registered, http://www.chictr.org.cn.
Electrolyte imbalance causes suppression of NK and T cell effector function in malignant ascites
Authors: Hrvat Antonio , Schmidt Mathias , Wagner Bernd , Zwanziger Denise , Kimmig Rainer , Volbracht Lothar , Brandau Sven , Mallmann-Gottschalk Nina
Published: September 2023

Background

Malignant ascites commonly occurs in advanced or recurrent stages of epithelial ovarian cancer during peritoneal carcinomatosis and is correlated with poor prognosis. Due to its complex composition of cellular and acellular components malignant ascites creates a unique tumor microenvironment, which mediates immunosuppression and promotes progression of disease. However, the immunosuppressive mechanisms remain poorly understood.

Methods

In the present study, we explored the antitumor activity of healthy donor NK and T cells directed against ovarian cancer cells in presence of malignant ascites derived from patients with advanced or recurrent peritoneal carcinomatosis. A wide range of methods was used to study the effect of ascites on NK and T cells (FACS, ELISA, EliSpot, qPCR, Live-cell and confocal microscopy, Western blot and electrolyte flux assays). The ascites components were assessed using quantitative analysis (nephelometry, potentiometry and clinical chemistry) and separation methods (dialysis, ultracentrifugal filtration and lipid depletion).

Results

Ascites rapidly inhibited NK cell degranulation, tumor lysis, cytokine secretion and calcium signaling. Similarly, target independent NK and T cell activation was impaired in ascites environment. We identified imbalanced electrolytes in ascites as crucial factors causing extensive immunosuppression of NK and T cells. Specifically, high sodium, low chloride and low potassium content significantly suppressed NK-mediated cytotoxicity. Electrolyte imbalance led to changes in transcription and protein expression of electrolyte channels and impaired NK and T cell activation. Selected inhibitors of sodium electrolyte channels restored intracellular calcium flux, conjugation, degranulation and transcript expression of signaling molecules. The levels of ascites-mediated immunosuppression and sodium/chloride/potassium imbalance correlated with poor patient outcome and selected molecular alterations were confirmed in immune cells from ovarian cancer patients.

Conclusion

Our data suggest a novel electrolyte-based mechanism of immunosuppression in malignant ascites of patients with peritoneal carcinomatosis. We show for the first time that the immunosuppression of NK cytotoxicity in coculture assays is correlated to patient poor survival. Therapeutic application of sodium channel inhibitors may provide new means for restoring immune cell activity in ascites or similar electrolyte imbalanced environments.
Amitriptyline overdose—an uncommon cause of acute transient exotropia presenting to the emergency setting: a case report
Authors: Rajaratnam Arun
Published: September 2023

Background

Acute presentations of acquired exotropia or divergent alignment of either or both eyes are commonly observed following intracranial vascular events, trauma, orbital, and endoscopic sinus surgeries.

Case presentation

The reported case is about a 16-year-old previously healthy Tamil female who presented to the emergency department with a few hours of reduced responsiveness. With the only clue in the history being about a family conflict the previous day, the examination revealed a noticeable exotropia along with a constellation of anticholinergic findings: a low Glasgow Coma Score, mydriasis, tachycardia, floppy limbs, exaggerated reflexes, and a palpable urinary bladder. Amitriptyline overdose leading to significant neurological involvement was suspected, and she was immediately offered urine alkalinization. Resources for urine and blood toxicological studies were not available. The patient gained consciousness 24 hours later and confirmed an overdose of ten amitriptyline tablets. Exotropia, a unique manifestation of this patient’s neurotoxicity, spontaneously resolved in 36 hours.

Discussion and conclusions

The reported case is about an uncommon clinical finding of exotropia seen in a common toxicological emergency: acute amitriptyline overdose. The importance of having a wide knowledge of various clinical presentations of drug toxicities is highlighted here, as any delay in diagnosis or initiation of life-saving measures could have resulted in fatal consequences.
Diplopia in a patient presenting with “blurred vision”: a case report
Authors: Harrison Anil , Mudhar Onkar , Yoo Jun , Rampal Mayank
Published: September 2023

Background

Myasthenia gravis is an autoimmune condition affecting the neuromuscular junction and causing muscle weakness along with fatigue (myasthenia). When the clinical manifestations of myasthenia gravis are isolated to the eye muscles, only causing weak eye movements, it is referred to as ocular myasthenia gravis, which can mimic a 1 and ½ syndrome.

Case presentation

An African-American female in her fifties with past medical history of hypertension presented to our outpatient clinic with complaints of blurred vision for two weeks. Her symptoms were associated with facial discomfort and a generalized headache. On physical examination upon her initial presentation, there was demonstratable swelling of the left upper eyelid with drooping. Her extraocular movements revealed defects with the abduction and adduction of the right eye, and the left eye would not adduct, although the outward movement was normal. The left eye failed to lift/elevate completely when looking upwards, a pseudo 1 and ½ syndrome. A positive Cogan lid twitch was also noticed. Imaging of the brain and orbit ruled out central causes. Diagnosis of ocular myasthenia gravis was made in accordance with positive anti-acetylcholine receptor antibodies. With 120 mg pyridostigmine oral dose, the patient experienced improvement subjectively and objectively, and the patient was discharged on oral pyridostigmine and prednisone. Six months later, with prednisone having been tapered off, the patient developed a myasthenic crisis and was treated with plasmapheresis and intravenous immunoglobulins. After recovering from the myasthenic crisis, efgartigimod infusions were instituted, which helped our patient restore normal life.

Conclusion

Our patient who presented with “blurred vision” was discovered to have binocular diplopia due to significant dysconjugate eye movements. After diligently ruling out central etiologies, we concluded that her presentation was due to a peripheral etiology. Her serologies and her presentation helped confirm a diagnosis of ocular myasthenia gravis. Also, as in most cases, our patient also progressed to develop generalized myasthenia gravis while on pyridostigmine. Efgartigimod infusions instituted after our patient recovered from a myasthenic crisis have helped her restore a normal life.
Challenges and opportunities of utilizing design thinking in the industry 4.0 era: based on the case study of industry wastewater treatment system development project process
Authors: Lee Hyejin , Zhang Yilei , Zhang Huihua , Liu Xuanchen
Published: September 2023

This paper reviews the research process conducted on developing a new system for industry wastewater treatment application to increase efficiency and sustainability by adopting industry 4.0 technology. The challenge of this project was to (a) utilize the design thinking methodology (human-centered design) entire process; (b) focus on heavy industry rather than the targeted user; and (c) adapt state of art technology. The objective was to revisit and invent new methods, such as metaphoric analysis, body thinking, and organization persona that would contribute to high-level innovative ideas: specifically, (a) the organization persona allowed to understand the dynamics of the complicated stakeholder structure; (b) the role of prototyping was mainly descriptive for communication; and (c) the case’s idea generation was used to affect the entire process of the project as well as benchmarking other industries. This paper attempts to address whether it is possible to create a new methodology that would address innovative business opportunities in complicated and high-tech adapting industries.
Gut microbes exacerbate systemic inflammation and behavior disorders in neurologic disease CADASIL
Authors: Liu Sheng , Men Xuejiao , Guo Yang , Cai Wei , Wu Ruizhen , Gao Rongsui , Zhong Weicong , Guo Huating , Ruan Hengfang , Chou Shuli , Mai Junrui , Ping Suning , Jiang Chao , Zhou Hongwei , Mou Xiangyu , Zhao Wenjing , Lu Zhengqi
Published: September 2023

Background

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a cerebral small vessel disease that carries mutations in NOTCH3. The clinical manifestations are influenced by genetic and environmental factors that may include gut microbiome.

Results

We investigated the fecal metagenome, fecal metabolome, serum metabolome, neurotransmitters, and cytokines in a cohort of 24 CADASIL patients with 28 healthy household controls. The integrated-omics study showed CADASIL patients harbored an altered microbiota composition and functions. The abundance of bacterial coenzyme A, thiamin, and flavin-synthesizing pathways was depleted in patients. Neurotransmitter balance, represented by the glutamate/GABA (4-aminobutanoate) ratio, was disrupted in patients, which was consistent with the increased abundance of two major GABA-consuming bacteria, Megasphaera elsdenii and Eubacterium siraeum. Essential inflammatory cytokines were significantly elevated in patients, accompanied by an increased abundance of bacterial virulence gene homologs. The abundance of patient-enriched Fusobacterium varium positively correlated with the levels of IL-1β and IL-6. Random forest classification based on gut microbial species, serum cytokines, and neurotransmitters showed high predictivity for CADASIL with AUC = 0.89. Targeted culturomics and mechanisms study further showed that patient-derived F. varium infection caused systemic inflammation and behavior disorder in Notch3R170C/+ mice potentially via induction of caspase-8-dependent noncanonical inflammasome activation in macrophages.

Conclusion

These findings suggested the potential linkage among the brain-gut-microbe axis in CADASIL.
Pyrroloquinoline quinone drives ATP synthesis in vitro and in vivo and provides retinal ganglion cell neuroprotection
Authors: Canovai Alessio , Tribble James R. , Jöe Melissa , Westerlund Daniela Y. , Amato Rosario , Trounce Ian A. , Dal Monte Massimo , Williams Pete A.
Published: September 2023

Retinal ganglion cells are highly metabolically active requiring strictly regulated metabolism and functional mitochondria to keep ATP levels in physiological range. Imbalances in metabolism and mitochondrial mechanisms can be sufficient to induce a depletion of ATP, thus altering retinal ganglion cell viability and increasing cell susceptibility to death under stress. Altered metabolism and mitochondrial abnormalities have been demonstrated early in many optic neuropathies, including glaucoma, autosomal dominant optic atrophy, and Leber hereditary optic neuropathy. Pyrroloquinoline quinone (PQQ) is a quinone cofactor and is reported to have numerous effects on cellular and mitochondrial metabolism. However, the reported effects are highly context-dependent, indicating the need to study the mechanism of PQQ in specific systems. We investigated whether PQQ had a neuroprotective effect under different retinal ganglion cell stresses and assessed the effect of PQQ on metabolic and mitochondrial processes in cortical neuron and retinal ganglion cell specific contexts. We demonstrated that PQQ is neuroprotective in two models of retinal ganglion cell degeneration. We identified an increased ATP content in healthy retinal ganglion cell-related contexts both in in vitro and in vivo models. Although PQQ administration resulted in a moderate effect on mitochondrial biogenesis and content, a metabolic variation in non-diseased retinal ganglion cell-related tissues was identified after PQQ treatment. These results suggest the potential of PQQ as a novel neuroprotectant against retinal ganglion cell death.
Establishment and characterization of a canine chondrosarcoma cell line: Mango
Authors: Wang Meilin , Wang Xiao , He Lixin , Gao Hongbo , Li Wenxuan , Feng Huili , Zhao Qingyuan , Zhang Wenwen , Li Chengzong , Zhang Bohan , Qiu Changwei
Published: September 2023

In the global progress of bone tumor research, established stable and long-lasting transgenic chondrosarcoma (CSA) cell lines are rare, mainly of murine and human origin, while the establishment of canine CSA cell lines has yet to be reported. This study established a canine CSA cell line to facilitate the basic clinical study of canine CSA. Fifty five cases of canine osteolytic disease were collected, and more than 10 bone tumor samples from dogs with typical clinical signs were used for primary cell culture. A cell line with stable passaging for more than 100 generations and mouse tumorigenic ability was successfully cultured. According to the clinical characteristics of the dog and the histopathological results of the primary tumor, CSA was diagnosed, and the CSA cell line was designated Mango. Immunohistochemical (IHC) results showed that the immunoreactivity of bone gamma-carboxyglutamate protein (BGLAP), secreted protein acidic and rich in cysteine (SPARC), alkaline phosphatase (ALPL), vimentin (VIM) and S100 were positive. However, the immunoreactivity of pan-cytokeratin (PCK), chromogranin A (CGA), and platelet endothelial cell adhesion molecule-1 (CD31) was negative. Immunofluorescence (IF) results showed that the protein expressions in the Mango cell line were consistent with the IHC identification of the primary tumor. The Mango cell line’s doubling time was 43.92 h, and the cell formation rate exceeded 20%. There were abnormal chromosome numbers, hetero staining with toluidine blue, and certain calcification abilities. It could be passaged stably and continuously without changing the cell morphology and characteristics. In vivo, the cells were successfully injected into the nude mice model with a tumorigenic rate of 100%. The immunophenotype of the xenograft tumor was consistent with that of the primary tumor. Therefore, we effectively established a canine CSA cell line. As a promising cell material, this cell line can be used to construct a tumor-bearing model conducive to the subsequent basic research of canine CSA. Moreover, because of its similarity to human CSA, the animal model of CSA is also indispensable for investigating human CSA.
Risk of Further Progression or Death Among Durable Progression-Free Survivors With Melanoma or Non–Small-Cell Lung Cancer in PD-1 Blockade Trials: Implications for Imaging Surveillance
Authors: Deng Lei , Jiang Changchuan , Attwood Kristopher , Zhao Joseph J. , Perimbeti Stuthi , Hu Chen , Puzanov Igor , Dy Grace K.
Published: September 2023

Two years after PD-1 antibody, imaging scans beyond every 3 months may be an option for patients with melanoma and NSCLC.
Uric Acid Is Not Associated With Cardiovascular Health in Youth With Type 1 Diabetes: SEARCH for Diabetes in Youth Study
Authors: South Andrew M , Rigdon Joseph , Voruganti Saroja , Stafford Jeanette M , Dabelea Dana , Marcovina Santica , Mottl Amy K , Pihoker Cate , Urbina Elaine M , Jensen Elizabeth T
Published: September 2023

Context

Uric acid's role in cardiovascular health in youth with type 1 diabetes is unknown.

Objective

Investigate whether higher uric acid is associated with increased blood pressure (BP) and arterial stiffness over time in adolescents and young adults with type 1 diabetes and if overweight/obesity modifies this relationship.

Methods

Longitudinal analysis of data from adolescents and young adults with type 1 diabetes from 2 visits (mean follow up 4.6 years) in the SEARCH for Diabetes in Youth multicenter prospective cohort study from 2007 to 2018. Our exposure was uric acid at the first visit and our outcome measures were the change in BP, pulse wave velocity (PWV), and augmentation index between visits. We used multivariable linear mixed-effects models and assessed for effect modification by overweight/obesity.

Results

Of 1744 participants, mean age was 17.6 years, 49.4% were female, 75.9% non-Hispanic White, and 45.4% had a follow-up visit. Mean uric acid was 3.7 mg/dL (SD 1.0). Uric acid was not associated with increased BP, PWV-trunk, or augmentation index over time. Uric acid was marginally associated with PWV-upper extremity (β = .02 m/s/year, 95% CI 0.002 to 0.04). The magnitude of this association did not differ by overweight/obesity status.

Conclusion

Among adolescents and young adults with type 1 diabetes, uric acid was not consistently associated with increased BP or arterial stiffness over time. These results support findings from clinical trials in older adults with diabetes showing that lowering uric acid levels does not improve cardiovascular outcomes.
Endogenous Glucose Production in Patients With Glycogen Storage Disease Type Ia Estimated by Oral D-[6,6-2H2]-glucose
Authors: Rossi Alessandro , Oosterveer Maaike H , van Dijk Theo H , Bleeker Aycha , Koehorst Martijn , Weinstein David A , Bakker Barbara M , Derks Terry G J
Published: September 2023

Context

Glycogen storage disease type Ia (GSDIa) is an inborn metabolic disorder characterized by impaired endogenous glucose production (EGP). Monitoring of patients with GSDIa is prioritized because of ongoing treatment developments. Stable isotope tracers may enable reliable EGP monitoring.

Objective

The aim of this study was to prospectively assess the rate of appearance of endogenous glucose into the bloodstream (Ra) in patients with GSDIa after a single oral D-[6,6-2H2]-glucose dose.

Methods

Ten adult patients with GSDIa and 10 age-, sex-, and body mass index–matched healthy volunteers (HVs) were enrolled. For each participant, 3 oral glucose tracer tests were performed: (1) preprandial/fasted, (2) postprandial, and (3) randomly fed states. Dried blood spots were collected before D-[6,6-2H2]-glucose administration and 10, 20, 30, 40, 50, 60, 75, 90, and 120 minutes thereafter.

Results

Glucose Ra in fasted HVs was consistent with previously reported data. The time-averaged glucose Ra was significantly higher in (1) preprandial/fasted patients with GSDIa than HV and (2) postprandial HV compared with fasted HV(P < .05). A progressive decrease in glucose Ra was observed in preprandial/fasted patients with GSDIa; the change in glucose Ra time-course was directly correlated with the change in capillary glucose (P < .05).

Conclusion

This is the first study to quantify glucose Ra in patients with GSDIa using oral D-[6,6-2H2] glucose. The test can reliably estimate EGP under conditions in which fasting tolerance is unaffected but does not discriminate between relative contributions of EGP (eg, liver, kidney) and exogenous sources (eg, dietary cornstarch). Future application is warranted for longitudinal monitoring after novel genome based treatments in patients with GSDIa in whom nocturnal dietary management can be discontinued.
Model-Based Analysis of IGF-I Response, Dosing, and Monitoring for Once-Weekly Somapacitan in Children With GH Deficiency
Authors: Kildemoes Rasmus J , Backeljauw Philippe F , Højby Michael , Blair Joanne C , Miller Bradley S , Mori Jun , Lyauk Yassine K
Published: September 2023

Context

Growth hormone (GH) replacement therapy improves longitudinal growth and adult height in children with GH deficiency (GHD). GH stimulates insulin-like growth factor (IGF)-I release, the biomarker used for monitoring GH activity during treatment.

Objective

This study aims to provide model-based insights into the dose–IGF-I responses of once-weekly somapacitan, a novel long-acting GH, compared with daily GH in children with GHD.

Methods

Analyses included dosing information and 1473 pharmacokinetic samples from 210 somapacitan-treated pediatric patients with GHD across 3 trials, including phase 1 (NCT01973244), phase 2 (NCT02616562; REAL 3), and phase 3 (NCT03811535; REAL 4), as well as 1381 IGF-I samples from 186 patients with GHD treated with somapacitan in REAL 3 and REAL 4. Pharmacokinetic/pharmacodynamic modeling to characterize somapacitan dose–IGF-I response and predict the response to dosing day changes.

Results

Relationships were established between somapacitan dose, exposure, change from baseline IGF-I SD score (SDS), and height velocity (HV). A linear model permitted the development of a tool to calculate estimated average weekly IGF-I exposure from a single IGF-I sample obtained at any time within the somapacitan dosing interval at steady state. In practice, the use of this tool requires knowledge of somapacitan injection timing relative to IGF-I sample collection timing. IGF-I SDS simulations support flexible dosing day changes while maintaining at least 4 days between doses.

Conclusion

We characterized the dose–IGF-I response of somapacitan in children with GHD. To support physicians in IGF-I monitoring, we present a practical guide about expected weekly average IGF-I concentrations in these patients and provide insights on dosing day flexibility.
Undiagnosed Factor VII Deficiency in Cardiac Surgery Complicated by Bleeding: A Case Report
Authors: Knio Ziyad O. , Ising Mickey S. , Yount Kenan W. , Tanaka Kenichi , McNeil John S.
Published: September 2023

Rare bleeding disorders in the perioperative period call for targeted resuscitation strategies. Factor VII deficiency, for instance, is often corrected with exogenous administration of recombinant factor VIIa. This activated clotting factor, initially designed for patients with hemophilia A or B with factor inhibitors, is gaining popularity as a salvage therapy for severe and persistent traumatic and surgical bleeding. This article describes the management of a cardiothoracic surgical patient with undiagnosed isolated factor VII deficiency who experienced significant postoperative bleeding which subsided after the administration of recombinant factor VIIa. In this case, EXTEM failed to detect a clotting factor deficiency.
French Military Neurosurgery: At Home and Abroad
Authors: Fawaz Rayan , Robert Philémon , Maison François-Léopold , Fouet Mathilde , Delmas Jean-Marc , Desse Nicolas
Published: September 2023

The origins of military neurosurgery are closely linked to those of neurosurgery in France and more particularly in Paris. The history of the field starts with its origins by 2 men, Thierry de Martel and Clovis Vincent. The first note about the creation of military neurosurgery was in 1942, when Marcel David was reassigned from the Sainte Anne Hospital to practice at the Val-de-Grâce Military Hospital. David trained the first military neurosurgeon. The field of military neurosurgery was subsequently developed at the Val-de-Grâce Military Hospital, at Sainte Anne Military Teaching Hospital in Toulon in 1990 and then at Percy Military Teaching Hospital in 1996. Over 29 military neurosurgeons were trained in these institutions. Since 2000, French military neurosurgeons have been deployed from France in the Mobile Neurosurgical Unit. This Mobile Neurosurgical Unit represents 12% of all medical evacuation of casualties categorized as the high dependency level. Neurosurgeons were able to adapt to asymmetrical wars, such as in the Afghanistan campaign where they were deployed in the Role 3 medical treatment facility, and more recently in sub-Saharan conflicts where they were deployed in forward surgical roles. To manage the increasing craniocerebral war casualties in the forward surgical team, the French Military Health Service Academy established a training course referred to as the “Advanced Course for Deployment Surgery” providing neurosurgical damage control skills to general surgeons. Finally, military neurosurgery is reinventing itself to adapt to future conflicts through the enhancement of surgical practices via the addition of head, face, and neck surgeons.
aristaless-like homeobox-3 is wound induced and promotes a low-Wnt environment required for planarian head regeneration
Authors: Akheralie Zaleena , Scidmore Tanner J. , Pearson Bret J.
Published: September 2023

The planarian Schmidtea mediterranea is a well-established model of adult regeneration, which is dependent on a large population of adult stem cells called neoblasts. Upon amputation, planarians undergo transcriptional wounding programs and coordinated stem cell proliferation to give rise to missing tissues. Interestingly, the Wnt signaling pathway is key to guiding what tissues are regenerated, yet less known are the transcriptional regulators that ensure proper activation and timing of signaling pathway components. Here, we have identified an aristaless-like homeobox transcription factor, alx-3, that is enriched in a population of putative neural-fated progenitor cells at homeostasis, and is also upregulated in stem cells and muscle cells at anterior-facing wounds upon amputation. Knockdown of alx-3 results in failure of head regeneration and patterning defects in amputated tail fragments. alx-3 is required for the expression of several early wound-induced genes, including the Wnt inhibitor notum, which is required to establish anterior polarity during regeneration. Together, these findings reveal a role for alx-3 as an early wound-response transcriptional regulator in both muscle cells and stem cells that is required for anterior regeneration by promoting a low-Wnt environment.
Tackling the lack of diversity in cancer research
Authors: Molina-Aguilar Christian , Robles-Espinoza C. Daniela
Published: September 2023

Despite the clear benefit of studying biological samples from diverse genetic backgrounds and geographical locations, our current knowledge of disease is mostly derived from the study of European-descent individuals. In the cancer field, this is reflected in the poor representation of African and Amerindian/Latino samples in most large public data repositories. This lack of diversity is due to several reasons, but here we focus on (1) the lack of support for studies on non-European populations that are performed in low- and middle-income countries (LMICs), and (2) unequal partnerships between scientists in LMICs and those in high-income countries. We argue that expanding access to research funding, increasing the participation of underrepresented scientists in editorial boards and international conferences, facilitating the publication of studies conducted in these countries, and properly acknowledging LMIC researchers' contributions in publications and grant applications will promote equity for scientists working in LMICs. We envisage that this will translate to more impactful research in these countries, which will include more samples from diverse populations. For the cancer field, this will broaden our understanding of pathomechanisms and may help to improve the treatment of patients from all backgrounds.
Thermal acclimation in a non-migratory songbird occurs via changes to thermogenic capacity, but not conductance
Authors: Schweizer Rena M. , Romero Abimael , Tobalske Bret W. , Semenov Georgy A. , Carling Matt D. , Rice Amber M. , Taylor Scott A. , Cheviron Zachary A.
Published: September 2023

Thermoregulatory performance can be modified through changes in various subordinate traits, but the rate and magnitude of change in these traits is poorly understood. We investigated flexibility in traits that affect thermal balance between black-capped chickadees (Poecile atricapillus) acclimated for 6 weeks to cold (−5°C) or control (23°C) environments (n=7 per treatment). We made repeated measurements of basal and summit metabolic rates via flow-through respirometry and of body composition using quantitative magnetic resonance of live birds. At the end of the acclimation period, we measured thermal conductance of the combined feathers and skins. Cold-acclimated birds had a higher summit metabolic rate, reflecting a greater capacity for endogenous heat generation, and an increased lean mass. However, birds did not alter their thermal conductance. These results suggest that chickadees respond to cold stress by increasing their capacity for heat production rather than increasing heat retention, an energetically expensive strategy.
Synthesis of a Two-dimensional Multi-functional Macromonomer and Oxygen Permselectivity of Its Supramolecular and Covalent Polymer Membranes
Authors: Cheng Kehan , Shinohara Ken-ichi , Higashimine Koichi , Teraguchi Masahiro , Kaneko Takashi , Aoki Toshiki
Published: September 2023

Although polymers having small micropores are promising for good gas permselective membranes, such polymers tend to have no membrane-forming ability. In this study, a polymer including micropores was synthesized from two-dimensional fully-conjugated macromonomer (2DM) with multi-acetylene and hydroxyl groups. In spite of the low molecular weight, its solvent-cast membrane (supra-poly(2DM)) showed good oxygen permselectivity. In addition, soluble high molecular weight network poly(2DM) membrane obtained from supra-poly(2DM) membrane showed higher oxygen permselectivity due to the increased number of micropores.
Evaluation of the efficacy and safety of percutaneous transforaminal endoscopic discectomy for multi-segmental lumbar disc herniation
Authors: Zhao Ya-fei , Tian Bin-wu , Ma Qiu-shuang , Zhang Meng
Published: September 2023

Objective: To investigate the clinical efficacy and safety of percutaneous transforaminal endoscopic discectomy (PTED) in the treatment of multi-segmental lumbar disc herniation (msLDH).

Methods: From January 2021 to December 2021, 75 patients with msLDH admitted to Baoding No.1 Hospital of Traditional Chinese Medicine were selected and divided into PTED group (n=40) and posterior lumbar interbody fusion (PLIF) group (n=35) according to different surgical methods. The operative time, intraoperative blood loss, surgical complications, Oswestry disability index (ODI) and Japanese Orthopedic Association score (JOA) scores were compared between the two groups.

Results: In the PTED group, the average operation time was 57.45±12.01minutes, and the average intraoperative blood loss was 50.57±16.69ml. There were three patients with surgical complications, including one case of hematoma, one case of aggravation of neurological symptoms and one case of new onset of neurological symptoms. In the PLIF group, there were 12 cases undergoing single-segment operation, 15 cases undergoing double-segment operation and 8 cases undergoing three-segment operation, the average operation time was 137.26±34.64minutes, and the average intraoperative blood loss was 456.06±33.06ml, there were four cases of wound fat liquefaction or delayed healing, two cases of hematoma, and three cases of exacerbation of original neurological symptoms or new neurological symptoms. At one month, six months, and one year of postoperative, the ODI and JOA scores of the two groups were significantly improved compared with those preoperative, and the ODI scores of the PTED group were better than those of the PLIF group (t=3.131, 2.263, 3.768, all P<0.05).

Conclusion: The surgical effect of PTED in the treatment of LDH is similar to that of PLIF. However, PTED has the advantages of short operation time, less blood loss, fewer surgical complications, and high surgical safety. It is worthy of clinical promotion.

doi: https://doi.org/10.12669/pjms.39.6.3399

How to cite this: Zhao Y, Tian B, Ma Q, Zhang M. Evaluation of the efficacy and safety of percutaneous transforaminal endoscopic discectomy for multi-segmental lumbar disc herniation. Pak J Med Sci. 2023;39(6):---------. doi: https://doi.org/10.12669/pjms.39.6.3399

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Effects of periodontal initial therapy combined with orthodontic treatment on anterior tooth function and inflammatory factors in gingival crevicular fluid in patients with periodontal disease induced anterior tooth displacement
Authors: Liu Yan , Shi Xie , Lin Gengbing , Guo Nan
Published: September 2023

Objective: To evaluate the effects of periodontal initial therapy combined with orthodontic treatment on anterior tooth function and inflammatory factors in gingival crevicular fluid in patients with periodontal disease induced anterior tooth displacement.

Methods: This was a clinical comparative study. A total of 140 patients with anterior teeth displacement caused by periodontal disease in Fujian University of Traditional Chinese Medicine from May 2020 to May 2022 were selected and randomly divided into two groups. Patients in the control group received periodontal initial therapy, and those in the study group were provided with orthodontic treatment on the basis of initial therapy. Further comparative analysis was performed focusing on the clinical effects of the two groups, the changes of probing depth, anterior overjet degree, oral function and inflammatory factors in gingival crevicular fluid before and after treatment.

Results: The efficacy of the study group was significantly higher than that of the control group(p=0.00). After treatment, the probing depth, the anterior overjet degree and the rate of bleeding on probing in the study group were significantly lower than those in the control group(P=0.00). Furthermore, the proportion of tooth mobility degrees I, II and III in the study group was significantly lower than that in the control group after treatment(P<0.05). The levels of post-treatment inflammatory factors in the study group were significantly lower than those in the control group(p=0.00).

Conclusion: Periodontal initial therapy combined with orthodontic treatment has a significant effect on anterior teeth displacement caused by periodontal disease, which deserves promotion clinically.

doi: https://doi.org/10.12669/pjms.39.6.7135

How to cite this: Liu Y, Shi X, Lin G, Guo N. Effects of periodontal initial therapy combined with orthodontic treatment on anterior tooth function and inflammatory factors in gingival crevicular fluid in patients with periodontal disease induced anterior tooth displacement. Pak J Med Sci. 2023;39(6):---------. doi: https://doi.org/10.12669/pjms.39.6.7135

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
The genome sequence of a solitary wasp, Mimumesa dahlbomi (Hymenoptera; Crabronidae; Pemphredoninae) (Wesmael, 1852)
Authors: Falk Steven , Monks Joseph ,   University of Oxford and Wytham Woods Genome Acquisition Lab,   Darwin Tree of Life Barcoding collective,   Wellcome Sanger Institute Tree of Life programme,   Wellcome Sanger Institute Scientific Operations: DNA Pipelines collective,   Tree of Life Core Informatics collective,   Darwin Tree of Life Consortium
Published: September 2023

We present a genome assembly from an individual female Mimumesa dahlbomi (solitary wasp; Arthropoda; Insecta; Hymenoptera; Crabronidae). The genome sequence is 297.3 megabases in span. Most of the assembly is scaffolded into 18 chromosomal pseudomolecules. The mitochondrial genome has also been assembled and is 20.66 kilobases in length. Gene annotation of this assembly on Ensembl identified 14,877 protein coding genes.
Organizational and methodological foundations of dissertation preparation
Authors: Ivanova Svetlana
Published: September 2023

The educational and methodological manual reveals the nature of pedagogical knowledge in the light of comparing the specifics of natural-scientific and humanitarian types of cognition, reveals milestones of methodological ideas about scientific cognition and modern features of dissertation research on pedagogy. As a specific methodological aid, the material on the choice of the research topic, tasks and organization of literature analysis on the topic is offered. The main part is presented with recommendations for the design of all the headings of the section "General characteristics of the work" (in the scientific community known as the methodological apparatus), "The main content of the work" (in the abstract), "Conclusion". Both those headings that are included in the current GOST and those that are not included in GOST, but are accepted in scientific research (additional elements of the methodological apparatus) are highlighted. In addition, the issues of organizing and conducting experimental work, problems of plagiarism, copyright and intellectual property law, scientific ethics, which are important for a novice researcher, are considered.
For postgraduates and doctoral students.
Psychology of the Russian people
Authors: Sevost'yanov Dmitriy
Published: September 2023

Russian Russian national (ethnic) psychology, the properties of the Russian national character are analyzed in the monograph; the reasons and ways of its formation, its historical and modern significance are considered. Special attention is paid to the contradictions that can be traced in the character of the Russian people, its strengths and weaknesses.
It is of interest to philosophers, sociologists, psychologists and other specialists in the field of humanities; it is addressed to students of all specialties and areas of training studying humanities, as well as to a wide range of readers.
Development of the service sector based on a customer-oriented approach
Authors: Gruzdeva Viktoriya , Gruzdev Georgiy , Klyueva Yuliya , Konova Vlada
Published: September 2023

In the monograph, the use of the civilizational paradigm of the analysis of economic processes and phenomena allows us to consider the specifics of the functioning of the hospitality industry in the conditions of the formation of the information economy. The features of the client-oriented approach in its institutional and dynamic dimensions are revealed. Special attention is paid to inclusive technologies in the field of hospitality.
The result of the analysis of the features of the formation of the institutional model of the hotel business in the Nizhny Novgorod region is presented. On the basis of a systematic approach, the entire process of functioning of a hospitality enterprise is considered from the standpoint of structural and functional dynamics. Special attention is paid to the analysis of the formation of the corporate culture of hotel and restaurant complexes in modern conditions.
It is intended for researchers, teachers, students studying in the areas of higher education 43.03.01 "Service", 43.03.02 "Tourism" and 43.03.03 "Hotel business", as well as for anyone interested in the problems of the development of the service sector in the conditions of the formation of information and cybernetic civilization.