bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonsyndromic Paucity of Interlobular Bile Ducts: Report of 10 Patients
Authors: Yehezkely‐Schildkraut Vered , Munichor Mariana , Mandel Hanna , Berkowitz Drora , Hartman Corina , Eshach‐Adiv Orly , Shamir Raanan
Published: January 2024

Objectives

Only a few reports of nonsyndromic paucity of interlobular bile ducts (NS‐PILBD) have been published. The authors' aim was to outline the clinical and laboratory profile of patients with NS‐PILBD diagnosed at a tertiary referral center.

Methods

The authors reviewed all the reports of pediatric liver biopsies performed between 1991 and 2000 at their institution. Upon diagnosis of NS‐PILBD, patients' records were examined for clinical, laboratory, and histologic data, and liver biopsy specimens were re‐evaluated.

Results

Three hundred biopsies were performed in children during the study period, of which 64 were in infants younger than 1 year. NS‐PILBD was diagnosed in 10 of 64 (16%) biopsy specimens. Mean age at presentation was 10 days (range, 1 day–6 weeks), and mean follow‐up was 4.5 years (range, 1–9 years). An underlying condition was identified in 70% of children with NS‐PILBD: namely congenital cytomegalovirus (n = 2), progressive familial intrahepatic cholestasis (PFIC, n = 2), mitochondrial DNA depletion (n = 1), Niemann‐Pick type C (n = 1), and arthrogryposis multiplex congenita, renal dysfunction, and cholestasis (ARC syndrome; n = 1). All children presented with jaundice. Four children had initially acholic stools. At their last follow‐up visit, failure to thrive was present in five children, and cholestasis in six children. Mortality was noted only in children with metabolic diseases (n = 2).

Conclusions

In the study, NS‐PILBD was common in young children undergoing liver biopsy. Although NS‐PILBD is nonspecific, a wide survey for inborn errors of metabolism should be included in the diagnostic work‐up of NS‐PILBD. In the authors' center, the association of certain metabolic diseases with NS‐PILBD carries a grave prognosis.
Fecal α1‐Antitrypsin Concentrations as a Measure of Enteric Protein Loss After Modified Fontan Operations
Authors: Fujii Tohru , Shimizu Toshiaki , Takahashi Ken , Kishiro Masahiko , Ohkubo Mataichi , Akimoto Katsumi , Yamashiro Yuichiro
Published: January 2024

Background

Little is known about the enteric protein loss in patients after a modified Fontan operation before the appearance of overt symptoms or signs of protein‐losing enteropathy (PLE). The authors examined the possibility of using fecal α1‐antitrypsin concentration measurements for the early detection of postoperative PLE and in longer term postoperative monitoring of these patients.

Methods

The authors compared fecal α1‐antitrypsin concentrations in stool samples from 12 children 12.0 to 43.7 months after modified Fontan operations with those of 12 age‐matched control subjects and examined the relationship between the α1‐antitrypsin levels and time since operation. The authors also compared fecal α1‐antitrypsin concentrations of stools from the same patients obtained at two different time points after surgery with intervals between samples ranging from 14.7 to 19.8 months.

Results

No significant differences in serum total protein and albumin levels were observed between patients after the modified Fontan operation and control subjects. The fecal concentrations of α1‐antitrypsin in patients after the Fontan operation were significantly (P < 0.01) higher than those in control subjects. There was no significant correlation between fecal α1‐antitrypsin concentrations and time elapsed after the Fontan operation. The fecal α1‐antitrypsin concentration increased significantly (P < 0.01) over periods of 14.7 to 19.8 months after the first measurement.

Conclusion

The results show that enteric protein loss begins before the appearance of hypoproteinemia in patients after a modified Fontan operation, and that the measurement of fecal α1‐antitrypsin concentrations in random stool samples is useful as an early indicator. To watch for the development of PLE after Fontan operation, it may be important to perform longitudinal follow‐up examinations of enteric protein loss by measuring fecal α1‐antitrypsin concentrations early in the postoperative period.
Acid Secretion From Birth to Adulthood
Authors: Boyle John T.
Published: January 2024

All infants, including premature infants as young as 24 weeks' gestational age, are able to maintain an intragastric pH below 4 from the first day of life. By 24 weeks, maximal acid output approaches that in adults. In adult studies, proton pump inhibitors (PPIs) are highly effective in relieving reflux symptoms and healing reflux esophagitis. Studies are needed to evaluate PPI efficacy and appropriate dosing in infants and children. Consequences such as hypergastrinemia, bacterial overgrowth, and other potential adverse events associated with long‐term PPI use also warrant evaluation in the pediatric population.
The Role of Lower Esophageal Sphincter Function and Dysmotility in Gastroesophageal Reflux in Premature Infants and in the First Year of Life
Authors: Davidson Geoffrey
Published: January 2024

Transient relaxations of the lower esophageal sphincter (tLESRs), but not delayed gastric emptying, are major mechanisms of gastroesophageal reflux in premature infants. These findings are similar to those seen in older children and adults with gastroesophageal reflux disease. Newer antireflux therapies should be developed that target the reduction of gastric acidity or reduction in the number of tLESRs.
Endoscopic Rectal Sparing in Children With Untreated Ulcerative Colitis
Authors: Rajwal Sanjay R. , Puntis John W. L. , McClean Patricia , Davison Suzanne M. , Newell Simon J. , Sugarman Ian , Stringer Mark D.
Published: January 2024

Background

Ulcerative colitis (UC) typically is associated with a confluent proctitis, whereas rectal sparing may be seen in large bowel Crohn disease (CD). A few studies have reported rectal sparing in UC and suggested that this might indicate a more severe form of the disease. This study aimed to determine the prevalence and prognostic significance of rectal sparing in children with newly diagnosed, untreated UC.

Methods

The records of all children with untreated UC presenting to a regional pediatric gastroenterology service between January 1996 and December 2001 were retrospectively reviewed. Patients were divided into two groups according to the endoscopic appearance of the rectum: Group 1 (proctitis) and Group 2 (rectal sparing). Clinical features, intractability index (duration of active disease as a proportion of length of follow‐up), response to treatment, relapse index (number of recurrences per year), and the need for surgery were compared.

Results

Thirty children with untreated UC were identified. Seven (23%) had rectal sparing at initial endoscopy, but disease distribution was otherwise similar in both groups. Presenting symptoms were similar in those with and without rectal sparing. In Group 1, 20 (87%) children achieved remission with initial medical treatment, compared with 3 (43%) in Group 2 (P < 0.05). The intractability index was higher in children with rectal sparing, but the difference was not statistically significant (P = 0.22). During a median follow‐up period of 2 years, one (4%) child in Group 1 and two (29%) children in Group 2 experienced primary sclerosing cholangitis, and two (29%) children with rectal sparing required colectomy, compared with none in Group 1.

Conclusions

Endoscopic rectal sparing was seen in 23% of children with newly diagnosed, untreated UC, but this feature did not correlate with presenting symptoms. However, the presence of rectal sparing may indicate more aggressive disease that is less responsive to medical treatment.
Gluten‐Free Diet Has a Beneficial Effect on Chromosome Instability in Lymphocytes of Children With Coeliac Disease
Authors: Kolaček Sanja , Jadrešin Oleg , Petković Iskra , Mišak Zrinjka , Sonicki Zdenko , Booth Ian Westerby
Published: January 2024

Objectives.

Children with coeliac disease (CD) have an increased number of chromosome aberrations in peripheral blood lymphocytes. Whether genetically determined or a secondary phenomenon in CD, chromosome abnormalities may be involved in the predisposition to cancer in CD patients. The aim of the study was to follow a group of children with CD in whom the initial frequency of chromosome aberrations at diagnosis was known and to measure the same variable after a minimum of 2 years on a gluten‐free diet.

Methods.

Chromosome aberrations in peripheral blood lymphocytes were determined in 17 patients with CD, before and after at least 24 months of a gluten free diet (mean, 33 months), and in 15 healthy children. The differences in the frequency of aberrations were analyzed by Mann‐Whitney U test and Wilcoxon matched‐pairs signed‐ranks test.

Results.

Twelve patients adhered to the diet and had a significantly lower frequency of chromosome aberrations than did 5 patients not following the diet (0.16%v 1.2%; P = 0.03), whereas at presentation there had been no difference (1.54%v 1.2%; P = 0.09). The frequency of aberrations at follow‐up in patients who were diet adherent was significantly lower than at presentation (1.54% v 0.16%; P = 0.02) and remained unchanged in patients who were not diet adherent (1.2%v 1.2%; P = 1). After at least 24 months of a gluten‐free diet, children with CD did not differ from healthy control subjects (0.16%v 0.27%; P = 0.54), whereas children not following the diet had an increased frequency of aberrations (1.2%v 0.27%; P = 0.05).

Conclusions.

The frequency of chromosome aberrations in peripheral blood lymphocytes of patients with CD decreased significantly on a gluten‐free diet. We conclude that genomic instability is a secondary phenomenon, possibly caused by chronic intestinal inflammation.
Serum Lipase After Secretin Stimulation Detects Mild Pancreatic Involvement in Cystic Fibrosis
Authors: Walkowiak Jaroslaw , Nousia‐Arvanitakis Sanda , Lisowska Aleksandra , Piotrowski Robert , Strzykala Krystyna , Bychowiec Bartosz , Songin Tomasz , Galli‐Tsinopoulou Assimina , Sands Dorota , Pidonia Ifigenia , Krawczynski Marian , Milanowski Andrzej , Herzig Karl‐Heinz
Published: January 2024

Background:

The assessment of severe pancreatic insufficiency in cystic fibrosis (CF) is not a diagnostic problem. However, identification of mild cases remains a challenge. The aim of this study was to assess the ability of serum lipase after secretin stimulation to identify mild pancreatic insufficiency in patients with CF.

Material and Methods:

Thirty patients with CF and pancreatic insufficiency (CF‐PI) and 30 patients with CF and pancreatic sufficiency (CF‐PS) were studied. Thirty healthy subjects with no known gastrointestinal disease served as controls. In all subjects, fecal fat excretion, fecal elastase‐1 (E1) concentration and basal and secretin‐stimulated serum lipase concentration were measured.

Results:

All patients with CF‐PI and 3 with CF‐PS had abnormally low fecal E1 concentrations. The remaining 27 CF‐PS patients and all controls had normal values. Basal and post‐stimulation lipase levels were extremely low in patients with CF‐PI. Mean basal and poststimulation serum lipase concentrations were significantly higher in CF‐PS who had normal fecal E1 concentrations but were still below those of controls (P < 0.001). Among the 27 CF‐PS patients with normal fecal elastase, high basal and poststimulation lipase values were found in 6 and 17 patients respectively.

Conclusion:

In patients with CF‐PS who have normal fecal elastase‐1 concentration, the measurement of basal or secretin‐stimulated lipase levels might be helpful in identifying the progression of the destructive process in the pancreas.
Biotherapeutic and Nutraceutical Agents: Working Group Report of the Second World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition
Authors: Yamashiro Yuichiro , Castaneda Carlos , Davidson Geoff , Gibson Glenn , Penna Francisco José , Mack David , Splawski Judy
Published: January 2024

Research

Characterize the taxonomy and features of candidate probiotics.

Determine the intestinal effects of probiotics: infectious diarrhea, necrotizing enterocolitis, inflammatory bowel diseases.

Determine extraintestinal effects: microflora manipulation, immunomodulation and allergy.

Intervention

Regulation and control of probiotic use as drugs through government agencies.

Application of good clinical practice guidelines to probiotic use.

Regulation and control of functional food and proper labelling.

Education

For physicians: what are probiotics and what are their specific indications.

For consumers: what is functional food and what can it do to improve health.
Celiac Disease and Other Immunologically Mediated Disorders of the Gastrointestinal Tract: Working Group Report of the Second World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition
Authors: Troncone Riccardo , Bhatnagar Shinjini , Butzner Decker , Cameron Don , Hill Ivor , Hoffenberg Edward , Maki Markku , Mendez Virginia , de Jimenez Mabel Zacur
Published: January 2024

Celiac Disease

Research

Treatment alternatives to the gluten‐free diet.

Definition of new diagnostic criteria.

Practical interventions to improve child health

Improved serologic testing.

Worldwide accepted definition of gluten‐free, labeling issues, availability and measures to monitor and assure compliance.

Educational needs and strategies to improve medical knowledge

Celiac disease awareness campaign

Food Allergy

Research

Identification of the whole spectrum of disorders due to food allergy.

Intervention

Identification and implementation of prevention strategies for food allergy.

Educational needs and strategies to improve medical knowledge

Diagnosis of food allergy, with a specific warning against non‐orthodox diagnostic tests.
Hepatic Failure and Liver Transplant: Working Group Report of the Second World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition
Authors: Baker Alastair , Alonso M. Estella , Aw Marion Margaret , Ciocca Mirta , Porta Gilda , Rosenthal Philip
Published: January 2024

Research

Definition(s) of acute liver failure in childhood.

Establish reliable predictive (prognostic) factors for acute liver failure.

Gain insight into the mechanisms that control proliferation of residual hepatocytes.

Intervention

Establish guidelines for the recognition of acute liver failure and optimal hospital management.

Establish an international committee to evaluate ethical aspects of obtaining materials and criteria to balance risk with benefit in treatment strategies devised to prevent liver transplantation.

Conduct randomized multicenter‐controlled trials to establish optimal use, indications and complications of liver support devices in acute liver failure.

Education

Provide primary health workers with guidelines for early recognition of acute liver failure and optimal hospital management including transfer to services with intensive care facilities and orthotopic liver transplantation.

Provide such guidelines with particular emphasis on treatments seen as harmless, and disseminate them to all health professionals likely to be involved with acute liver failure.
Perinatal Nutrition and Gastrointestinal Disorders: Working Group Report of the Second World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition
Authors: Kleinman Ronald E. , Berseth Carol , Castillo‐Duran Carlos , Cleghorn Geoffrey , Devane Sean , Garcia Rafael Jimenez , Ng Steven , Sanabria Marta Cristina
Published: January 2024

Research

Promote investigation into the effects of perinatal nutrition upon long‐term health outcomes.

Identify the optimal composition of enteral formulas and parenteral nutrition solutions to meet the needs of pre‐ and full‐term infants.

Investigate the development of intestinal motility in human infants and altered motility in infancy, including better methods of diagnosis and treatment.

Intervention

Support home‐based nutritional management of chronic nutritionally debilitating illnesses during the perinatal period.

Support and encourage breastfeeding at least through the first birthday and promote dietary supplementation or fortification (according to evidence based recommendations) with trace minerals and vitamins during the pre‐ and perinatal period (zinc, folic acid, iodine, iron) in at‐risk mothers and infants.

Encourage optimal nutritional management of very low birth weight infants and infants that have undergone major surgical interventions.

Education

Enhance the integration of the nutrition curriculum into the medical school curriculum and encourage the further exchange of knowledge among perinatal nutrition experts through joint workshops and scientific meetings.

Promote the use of effective means of communications, including electronic media, to disseminate information about perinatal nutrition, including the demonstrated benefits of breastfeeding, to health care professionals and parents.
Immunoregulation in the Liver and Its Extrahepatic Relevance
Authors: O’Farrelly Cliona
Published: January 2024

As well as being a metabolic factory, the liver also functions as a powerful immune organ constantly engaged in local immune responses. In addition, it has a significant influence on systemic immunity. The hepatic immune system recognises and responds to pathogens, as well transformed and metastatic cells, while at same time tolerising harmless dietary and commensal antigens. The molecular mechanisms by which these different discriminatory, regulatory and effector functions are mediated are only now beginning to be identified.
Prospective Population Screening for Celiac Disease: High Prevalence in the First 3 Years of Life
Authors: Castaño Luis , Blarduni Elisabeth , Ortiz Lourdes , Núñez Javier , Bilbao J. Ramón , Rica Itxaso , Martul Pedro , Vitoria Juan C.
Published: January 2024

Background:

Celiac disease (CD) is an autoimmune enteropathy that develops in genetically susceptible individuals exposed to gliadin. Early diagnosis of CD may reduce the risk of complications, and several studies have related the duration of gluten exposure to the risk of other autoimmune diseases. It has been proposed that silent CD be diagnosed as soon as possible to avoid potential complications.

Objectives:

The purpose of this study was to determine the prevalence of CD among children less than 3 years and to provide treatment to those patients diagnosed with CD.

Patients and Methods:

Parents of 1100 healthy children born between October 1998 and December 1999 were asked at the time of delivery to enroll their children in a program for the early diagnosis of CD. The parents of 830 children agreed to participate. Patients in the study were examined and anti–tissue transglutaminase antibody was first measured at about 1.5 years of age. A second antibody titer was obtained at about 2.5 years of age. Patients with detectable autoantibodies underwent intestinal biopsy for confirmation of CD.

Results:

Of the 830 children initially enrolled, 613 and 484 returned for the first and second visits, respectively. None had anti–tissue transglutaminase antibodies at the first visit, but 9 had anti–tissue transglutaminase immunoglobulins at the second visit. In 7 of these 9, intestinal biopsy confirmed the diagnosis of CD which suggests a minimum prevalence of CD of 1 per 118 healthy newborns.

Conclusions:

The authors observed a very high prevalence of CD, comparable to that observed in other European populations, which might even be higher if all of the children initially examined had returned for their second visit. If general screening for CD were accepted, the authors would recommend age 2–3 years as the best time for measuring tissue transglutaminase antibodies.
PF452 RUNX1 EXPRESSION IN NG2+ PERIVASCULAR CELLS IS REQUIRED FOR PROPER AORTIC EMBRYONIC HAEMATOPOIETIC ACTIVITY IN VIVO
Authors: Gonzalez Galofre Z.N. , Ventura T. , Crisan M.
Published: December 2023

Background:

Insight into the role of the niche in which the first haematopoietic stem cells (HSCs) emerge in vivo is still lacking. These adult‐type HSCs are generated in the ventral wall of the dorsal aorta within the aorta‐gonad‐mesonephros (AGM) region. In the bone marrow, HSCs are mainly located in close association with blood vessel walls. Cells expressing NG2, a cell surface proteoglycan found in both vasculogenic and angiogenic vasculature, have been shown to support adult HSC maintenance. Whether NG2+ cells also control HSC generation in the mouse embryo is still unknown. NG2 expression in the aortic mural cells starts shortly before HSC generation, and some NG2+ cells also express Runx1, a key haematopoietic transcription factor required for HSC generation.

Aims:

To investigate whether NG2+Runx1+cells control embryonic haematopoiesis in vivo.

Methods:

Runx1 was deleted in NG2 expressing cells by crossing Runx1fl/fl mice with mice containing a Cre transgene under the NG2 promoter. In vitro and in vivo functional assays were performed in E10 and E11 mouse embryos to assess haematopoietic activity. Three‐dimensional (3D) confocal imaging of the intact aorta was further used to confirm our results. To investigate whether NG2+ and NG2+Runx1+ cells are haematopoietic and/or haematopoietic precursors, cell sorting and colony‐forming assays were carried out on WT, Runx1 GFP and NG2Cre‐TdTomato transgenic mice.

Results:

By 3D confocal imaging, we found that intra‐aortic haematopoietic clusters are dramatically reduced in number in homozygous KO mouse embryos (NG2Cre:Runx1fl/fl) compared to WT (NG2+:Runx1fl/+) controls. This was further confirmed by functional in vitro and in vivo assays. Both haematopoietic progenitors and haematopoietic stem cell activities are affected in the KO AGM. Depletion of Runx1 in NG2+ cells drastically impairs all haematopoietic progenitor numbers in the dorsal aorta of both E10.5 and E11 mouse embryos and, in vivo, KO AGM had a reduced capacity of reconstituting adult irradiated recipient mice. NG2+ cells (or NG2+Runx1+) are not haematopoietic nor haematopoietic precursors suggesting that NG2+Runx1+ cells act as a supportive niche for haematopoietic progenitor and stem cell generation at this stage.

Summary/Conclusion:

In conclusion, Runx1 expression in the hematopoietic niche is required prior to HPSC generation in the mouse embryo in vivo. Ongoing experiments aim to test whether this is time‐ and organ‐dependent.
PF460 SINGLE CELL RNASEQ REVEALS THE IN VIVO DIFFERENTIATION POTENTIAL AND TRANSCRIPTIONAL DYNAMICS OF IMMATURE HUMAN THYMOCYTES
Authors: Lavaert M. , Vandamme N. , Saeys Y. , Taghon T.
Published: December 2023

Background:

T cell development depends on the colonization of the thymus by multipotent progenitor cells from the bone marrow. There, these precursor cells are gradually reprogrammed into committed T cell progenitors that have lost the developmental potential towards other hematopoietic lineages. While lineage tracing experiments in mice have provided evidence to which non T‐cell lineages these early T cell precursors differentiate in vivo, it remains unclear in human which blood cell lineages can originate from early T cell precursors. In vitro differentiation experiments have revealed erythroid, myeloid (DC, monocyte, granulocyte) and lymphoid (B, T, NK) differentiation potential, but whether this occurs in vivo is not clear.

Aims:

While lineage tracing experiments in mice have provided evidence to which non T‐cell lineages these early T cell precursors differentiate in vivo, it remains unclear in human which blood cell lineages can originate from early T cell precursors. In vitro differentiation experiments have revealed erythroid, myeloid (DC, monocyte, granulocyte) and lymphoid (B, T, NK) differentiation potential, but whether this occurs in vivo is not clear.

Methods:

Therefore, we have performed single cell RNA sequencing on more than 70.000 human CD34+lin‐ thymocytes that comprise the most immature thymocyte fraction of the human pediatric thymus.

Results:

Analysis of this dataset showed that cell cycle constitutes the majority of variation in the dataset, indicating less heterogeneity than anticipated. Indeed, using a strategy in which both clustering and trajectory inference were used, only limited branching was observed towards other, non T‐cell hematopoietic lineages, indicating a discrepancy between reported developmental potential and in vivo cell fate. Using these branching events, commitment was traced to coincide with loss of CD44 expression, confirming recent findings. In addition, we used CITEseq to correlate previously defined immature thymocyte subsets to these newly defined developmental cell states.

Summary/Conclusion:

In conclusion, our work suggests that the in vivo differentiation of immature human thymocytes is much more restricted compared to what in vitro differentiation experiments have suggested. In addition, we have delineated the transcriptional events that define the transition from multipotency toward T‐cell lineage commitment at the single cell level and redefine immature thymocyte subsets in human.
PF478 DOES ESCALATED BEACOP‐DACARBAZINE DO THE SAME AS ESCALATED BEACOP‐PROCARBAZINE FOR UNFAVORABLE HODGKIN'S LYMPHOMA?
Authors: Mansouri R. , Kacem K. , Jabr D. , Bchir M. , Aissaoui L. , Berred E. , Kefi S. , Ben Néji H. , Achour M. , Ben Abdennebi Y. , Bahri M. , Meddeb B. , Ben Lakhal R.
Published: December 2023

Background:

The management of Tunisian Adult Hodgkin's lymphoma (HL) has been standardized since 1999. Since 2008 we individualized four therapeutic groups according age, stage (Ann Arbor), EORTC criteria and GHSG criteria. So for patients aged less than 60 years we considered unfavorable group who have advanced stage III‐IV Ann Arbor and II stage with large mediastinal mass. This group received the escalated BEACOPP (esc‐BEACOPP) protocol differently to other three groups.

Aims:

We report in this study the therapeutic results of the national protocol of Adult HL (MDH2015) for this group and demonstrate the place of Dacarbazine.

Methods:

Our study is prospective monocentric interesting 76 patients followed between June 2015 and December 2017 for HL stage III‐IV and stage II with large mediastinal mass and treated according MDH2015 protocol. The median age was 29 years [14–58 years].B symptoms were found in 67% of our patients. Our patients were stage III‐IV Ann Arbor in 83% of cases and stage II with large mediastinal mass in 17%. For advanced stage, 68% of patients have IPS>2. The MDH 2015 protocol is based on a strategy adapted to the therapeutic response to 2 cycles of esc‐BEACOPP. We considered as a primary failure, patients hadn’t achieved response≥75% after 4 cycles of esc‐BEACOPP.Our patients had received in this protocol Dacarbazine 250 mg/m2 three days/cycle instead of Procarbazine (esc‐BEACOPD).

Results:

Response≥75% to 2 courses of esc‐BEACOPD was achieved in 43% of patients and the response rate at the end of treatment was 92%. Fourteen patients (19%) had primary failure. In the multivariate analysis, the advanced stage Ann Arbor (III‐IV) and response<75% after 2 cycles of esc‐BEACOPD were an independent predictive factor of primary failure, with respectively p = 0.01 and p < 0.001. The relapse rate was 10%. The median follow‐up was 25 months [5–46 months]. Event free survival (EFS), relapse free survival (RFS) and overall survival (OS) at 2 years were respectively, 77%, 90% and 90%. In multivariate analysis, the prognostic factors for poor OS were large mediastinal mass (p = 0.05), response<75% at 2 courses (p = 0.04). The EFS is better without large mediastinal mass (p = 0.03) and without lymphopenia (p = 0.02). Fifty per cent of neutropenia was happened. Febrile neutropenia was noted in 24% of cases. No treatment related mortality was noted.

Summary/Conclusion:

Compared to MDH 2008 (third version of Tunisian prospective protocol), the use of Dacarbazine instead of Procarbazine is equally effective in term of response rate and the survivals (EFS, RFS and OS). The toxicity is the same.
気胸，膿胸を合併し胸腔鏡手術が有効であったLemierre症候群の1例(Pneumothorax and empyema secondary to Lemierre’s syndrome treated by thoracoscopic surgery)
Authors: 由希子 下茂 , 徹 瀧口 , 史英 金 , 太吾 阪本 , 陽介 佐藤 , 佳之 松本 , 將司 横堀
Published: January 2024

症例は既往のない29歳の男性。咽頭痛を主訴に近医を受診し，扁桃炎の診断であった。1週間後に著明なSpO2の低下を認め，集中治療目的に当科を紹介受診した。造影CTで口腔内膿瘍，左内頸静脈に血栓性静脈炎，両肺野に多数の結節影，両側の大量胸水を認めた。口腔内膿瘍の穿刺液，血液，胸水の培養からはいずれもFusobacterium necrophorumが同定された。先行する口腔咽頭感染，血栓性静脈炎，遠隔感染巣，血液培養陽性からLemierre症候群と診断した。人工呼吸器管理開始直後，両側気胸となり，酸素化の安定に時間を要した。また，その後膿胸の管理に難渋し，両側に計5本のドレーンを挿入して胸腔内の洗浄を繰り返した。左側の気胸と膿胸の改善に乏しく，第15病日に胸腔鏡補助下に洗浄ドレナージ術とドレーン位置の調整を行った。第50病日にすべてのドレーンを抜去でき，第56病日にリハビリテーション病院へ転院となった。気胸，膿胸の再発はなく社会復帰した。Lemierre症候群は，口腔，咽頭領域の先行感染を契機に発症し，炎症が波及して内頸静脈の血栓性静脈炎や遠隔臓器への敗血症性塞栓症を引き起こす重篤な全身感染症である。高頻度に敗血症性肺塞栓症を合併するため，陽圧換気による気胸発症に注意が必要である。また，合併する気胸や膿胸は難治性であることが多く，本症例では胸腔鏡を用いたドレナージが有効であった。

下茂由希子と滝口徹は筆頭著者として同等の貢献をした。
Immune infiltration is associated with pan‐cancer prognostic biomarker RING finger protein 187
Authors: Fan Xin‐Tong , Gao Bing‐Fang , Wang Xiao‐Fei , Zhou Kai , Zhao Ying , Yuan Jie
Published: January 2024

Cancer is associated with the highest mortality rate globally. While life‐saving screening and treatments exist, better awareness is needed. RNF187, an E3 ligase regulating biological processes, belongs to the RING domain‐containing E3 ligase family. RNF187 may serve as an oncogene due to abnormal expression in tumors. However, its association with immune infiltration and prognosis across various cancers remains unclear. We searched several databases including TCGA, GTE x, CCLE, TIMER, and GSEA. R software was used to evaluate RNF187 differential expression, survival, pathology stage, DNA methylation, tumor mutational burden (TMB), microsatellite instability (MSI), gene co‐expression analysis, mismatch repairs (MMRs), tumor microenvironment (TME), and immune cell infiltration. Clinicopathological data were collected, and immunohistochemistry was used to verify RNF187 expression in tumor tissues. RNF187 expression was up‐regulated in various cancers compared to that in normal tissues and associated with poor patient outcomes. Dysregulation of RNF187 expression in multiple cancer types was strongly correlated with DNA methylation, MMR, MSI, and TMB. RNF187 could interact with different immune cells in cancers. Biomarkers associated with RNF187 may be helpful for prognosis and immunology in treating pan‐cancer patients.
A high‐order shell finite element for the large deformation analysis of soft material structures
Authors: Pagani A. , Augello R. , Carrera E.
Published: January 2024

This work proposes a higher‐order unified shell finite element for the analysis of cylinders made of compressible and nearly incompressible hyperelastic materials. The nonlinear governing equations are derived employing the Carrera unified formulation (CUF), thanks to which it is possible to build shell elements with the capability to capture three‐dimensional (3D) transverse and out‐of‐plane effects. The material and geometric nonlinearities are expressed in an orthogonal curvilinear reference system and the coupled formulation of hyperelastic constitutive law is considered. The principle of virtual work and a total Lagrangian approach is used to derive the nonlinear governing equations, which are solved by a Newton–Raphson scheme. The numerical investigations deal with a curved arch and both thick and thin cylinders subjected to line and point loadings. The obtained results are validated by comparing them with those from the literature. They demonstrate the reliability of the proposed method to analyze compressible and incompressible hyperelastic shell structures.
Rapid assessment of wetting of natural fiber surfaces by biodegradable copolyester using spectroscopic and microscopic techniques
Authors: Giri Jyoti , Henning Sven , Lach Ralf , Grellmann Wolfgang , Bledzki Andrzej K. , Adhikari Rameshwar
Published: December 2023

A biodegradable polymer, the poly(butylene adipate co‐terephthalate) (PBAT), was compounded with the microcrystalline cellulose (MCC) obtained from different sources (such as wheat stalk and rice husk powder) to prepare the polymer composites. The two components, here found to be compatible, as evidenced by the Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM). Further assessment of the compounded fibers with the organic solvent, the toluene, illustrated the nature of the wetting phenomena of MCC by PBAT. The SEM observation showed the wrapping of the PBAT layer onto the MCC phase after the removal of the polymer matrix. The FTIR spectrum showed the presence of the PBAT carbonyl peak on extracted fibers from the composite via solvent removal. It could be concluded that the PBAT could wet the MCC effectively in the composites suggesting the potential of enhancing their properties.

Highlights

A biodegradable polymer, the PBAT, melt‐mixed with plant‐based natural fiber.

The fiber in composites was found to be wetted with the PBAT layer.

H‐bonding between the CO group of PBAT and the OH group of fiber caused wetting.

Raw, processed, and silane‐treated fibers showed similar wetting phenomena.
Der Einbrennvorgang des Bethe‐Weizsäcker‐Zyklus
Authors: Bemmerer Daniel , Rümmler Simon , Herrera Yago
Published: January 2024

Das Wasserstoffbrennen in der Sonne wird von der sogenannten Proton‐Proton‐Kette bestimmt. Ein zweiter, parallel ablaufender Prozess ist der Bethe‐Weizsäcker‐ oder CNO‐Zyklus. Bei der Sonne trägt er nur etwa 0,8 % zur Energieerzeugung bei, kann aber zur Bestimmung der Kohlenstoffhäufigkeit im Sonneninnern genutzt werden. Neue Labordaten zur ersten Reaktion im Zyklus zeigen für massereiche Sterne eine 25 % geringere Rate als bislang angenommen, während sich für unsere Sonne wenig ändert.
Die Entdeckung des Unsichtbaren: Optik und Mikrobiologie in E. T. A. Hoffmanns „Meister Floh“
Authors: Heydenreich Aura
Published: January 2024

E. T. A. Hoffmanns Prosa mutet wie ein Kaleidoskop optischer Medien an, sein Werk steht im diskursiven Umfeld eines Umbruchs in der Geschichte des Sehens und der Beobachtung.
The mineralocorticoid receptor forms higher order oligomers upon DNA binding
Authors: Fettweis Gregory , Johnson Thomas A. , Almeida‐Prieto Brian , Weller‐Pérez Julián , Presman Diego M. , Hager Gordon L. , Alvarez de la Rosa Diego
Published: December 2023

The prevailing model of steroid hormone nuclear receptor function assumes ligand‐induced homodimer formation followed by binding to DNA hormone response elements (HREs). This model has been challenged by evidence showing that the glucocorticoid receptor (GR) forms tetramers upon ligand and DNA binding, which then drive receptor‐mediated gene transactivation and transrepression. GR and the closely‐related mineralocorticoid receptors (MR) interact to transduce corticosteroid hormone signaling, but whether they share the same quaternary arrangement is unknown. Here, we used a fluorescence imaging technique, Number & Brightness, to study oligomerization in a cell system allowing real‐time analysis of receptor‐DNA interactions. Agonist‐bound MR forms tetramers in the nucleoplasm and higher order oligomers upon binding to HREs. Antagonists form intermediate‐size quaternary arrangements, suggesting that large oligomers are essential for function. Divergence between MR and GR quaternary structure is driven by different functionality of known and new multimerization interfaces, which does not preclude formation of heteromers. Thus, influencing oligomerization may be important to selectively modulate corticosteroid signaling.
A complex network of interdomain interactions underlies the conformational ensemble of monomeric TDP‐43 and modulates its phase behavior
Authors: Mohanty Priyesh , Rizuan Azamat , Kim Young C. , Fawzi Nicolas L. , Mittal Jeetain
Published: December 2023

TAR DNA‐binding protein 43 (TDP‐43) is a multidomain protein involved in the regulation of RNA metabolism, and its aggregates have been observed in neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Numerous studies indicate TDP‐43 can undergo liquid–liquid phase separation (LLPS) in vitro and is a component of biological condensates. Homo‐oligomerization via the folded N‐terminal domain (aa:1–77) and the conserved helical region (aa:319–341) of the disordered, C‐terminal domain is found to be an important driver of TDP‐43 phase separation. However, a comprehensive molecular view of TDP‐43 phase separation, particularly regarding the nature of heterodomain interactions, is lacking due to the challenges associated with its stability and purification. Here, we utilize all‐atom and coarse‐grained (CG) molecular dynamics (MD) simulations to uncover the network of interdomain interactions implicated in TDP‐43 phase separation. All‐atom simulations uncovered the presence of transient, interdomain interactions involving flexible linkers, RNA‐recognition motif (RRM) domains and a charged segment of disordered C‐terminal domain (CTD). CG simulations indicate these inter‐domain interactions which affect the conformational landscape of TDP‐43 in the dilute phase are also prevalent in the condensed phase. Finally, sequence and surface charge distribution analysis coupled with all‐atom simulations (at high salt) confirmed that the transient interdomain contacts are predominantly electrostatic in nature. Overall, our findings from multiscale simulations lead to a greater appreciation of the complex interaction network underlying the structural landscape and phase separation of TDP‐43.
Extrapleural air secondary to idiopathic pulmonary fibrosis‐related pneumomediastinum
Authors: Nagata Yuichi , Watanabe Takayasu , Tanabe Yuki , Kato Motoyasu , Shukuya Takehito , Seyama Kuniaki , Takahashi Kazuhisa
Published: January 2024

Key message

Extrapleural air is a rare condition that may concurrently develop with pneumomediastinum and pneumothorax, especially in older patients with fragile connective tissues. Physicians should consider extrapleural air to prevent inadvertent harm. Coronal reconstruction computed tomography images help appreciate extrapleural air and recognize the track of extrapulmonary air.
i‐MYO: A multi‐grasp prosthetic hand control system based on gaze movements, augmented reality, and myoelectric signals
Authors: Shi Chunyuan , Zhao Jingdong , Yang Dapeng , Jiang Li
Published: December 2023

Background

Controlling a multi‐grasp prosthetic hand still remains a challenge. This study explores the influence of merging gaze movements and augmented reality in bionics on improving prosthetic hand control.

Methods

A control system based on gaze movements, augmented reality, and myoelectric signals (i‐MYO) was proposed. In the i‐MYO, the GazeButton was introduced into the controller to detect the grasp‐type intention from the eye‐tracking signals, and the proportional velocity scheme based on the i‐MYO was used to control hand movement.

Results

The able‐bodied subjects with no prior training successfully transferred objects in 91.6% of the cases and switched the optimal grasp types in 97.5%. The patient could successfully trigger the EMG to control the hand holding the objects in 98.7% of trials in around 3.2 s and spend around 1.3 s switching the optimal grasp types in 99.2% of trials.

Conclusions

Merging gaze movements and augmented reality in bionics can widen the control bandwidth of prosthetic hand. With the help of i‐MYO, the subjects can control a prosthetic hand using six grasp types if they can manipulate two muscle signals and gaze movement.
Electrochemical Investigations of Plant Response to Salt Stress: Insights Through Impedance Studies of OECT‐Based Biosensor
Authors: M Sneha , Ravindranath Nair Afijth , Jayaraman V.
Published: January 2024

Organic Electrochemical Transistor fabricated from conducting polymer material, PEDOT: PSS has been demonstrated towards study of plant response to salt stress. Electrochemical impedance spectroscopic studies of OECT under both in‐vivo and in‐vitro salt stress monitoring conditions have been carried out. Change in ionic concentration induced in the biological system of a living plant subjected to salt stress has been elucidated in terms of change in impedance of biosensor integrated in its stem. The impedance data recorded was used to derive equivalent distributed‐element circuit models for the device, under both in‐vivo and in‐vitro conditions.
Microfluidic Encapsulation of Vorinostat in Calcium Alginate Microparticles: Prolonged Release and Enhanced in vitro Cytotoxicity
Authors: Dang Cu Trung , Dang Trung Dung , Thi Thuy Trang Ngo , Tran Duy Thanh , Nguyen Lan Huong , Kim Gyu Man , Ta Hong Duc , Tran Khac Vu
Published: January 2024

In this research, the vorinostat‐loaded alginate microparticles were created and their characterization was performed using scanning electron microscopy (SEM), energy‐dispersive X‐ray mapping (EDX‐mapping), and transmission electron microscopy (TEM). Differential scanning calorimetry (DSC) was used to assess the drug state and thermal behavior of vorinostat within the microparticles. The encapsulation efficiency and loading efficiency were determined, and the solubility of vorinostat in the microparticles was investigated. In vitro drug release studies demonstrated sustained release of vorinostat from the microparticles. The cytotoxicity of vorinostat‐loaded alginate microparticles was evaluated using HepG2, MCF‐7, and SK‐LU‐1 cell lines. The results indicated significant inhibition of cell growth, and the IC50 values were estimated. Overall, this study successfully demonstrated the fabrication of vorinostat‐loaded alginate microparticles using a microfluidic approach, suggesting a simple and effective delivery system for vorinostat with improved physicochemical and pharmacological properties.
Rational Design and Site‐Directed Mutagenesis Promote the Heterologous Production of the Antitumor Natural Product Dehydroabietic Acid
Authors: Ma Lin , Gao Jie , Qiu Yufan , Liu Yuan , Wu Xiaoyi , Zhang Xianan , Tong Yuru , Gao Wei , Zhang Yifeng , Liu Changli
Published: January 2024

Cytochrome P450s participate in the biosynthesis of natural active ingredients and catalyze the formation of hydroxyl, carboxyl, epoxy and other groups from C−H bonds. CYP728B70 from Tripterygium wilfordii oxidizes the miltiradiene‐C18 methyl group to produce dehydroabietic acid, a diterpenoid intermediate with anticancer, antibacterial and anti‐inflammatory activities. To elevate the carboxylation product output, we excavated serveral homologous CYP728Bs and an N‐terminal truncated CYP728B70 transcript from T. wilfordii genome, of which CYP728B79 possessed a weak carboxylation effect towards miltiradiene through heterologous expression in Saccharomyces cerevisiae. We employed RoseTTAFold method and molecular dynamic simulations to predict its protein structure and docking pose of CYP728B70, and obtained several mutants with increased yield using Funclib and site‐directed mutagenesis methods. Our study confirmed the influence of peripheral residues on protein activity, improved the catalytic activity of CYP728B70, and would provide ideas for related enzyme modification.
Direct Reduction of Iron Ore Pellets by Using CO/CO2 and CO Gases
Authors: Lu Yu‐Chiao , Karasev Andrey , Ersson Mikael
Published: December 2023

Gas‐based direct reduction in a shaft furnace is the dominant process in the world for production of direct reduced iron. As fresh reducing gas passes through the iron ore burden, it is diluted by the gas emitted from the reacted iron ores which decreases the reduction potential of the reducing gas. Previous reduction experiments mostly used single pellet which could not examine this phenomenon. In this study, hematite pellets arranged in multiple layers inside a molybdenum basket are reduced isothermally at 1173–1273 K using 50% CO + 50% CO2% and 100% CO gases under flow rates of 0.2–5.0 NL min−1 to simulate the dilution of CO by CO2 in the shaft. It is discovered that the reduction of pellets in the basket is highly uneven even in pure CO atmosphere. Pellets in the middle layer are reduced ≈2 times less than the pellets in the top and bottom layers. The top side of a pellet is also less reduced than the bottom side facing the gas inlet. During melting of incompletely reduced pellets at 1873 K, intensive interaction between the unreduced iron oxides and the alumina crucible was observed. Thus, smelting of incompletely reduced iron could potentially shorten the refractory lifetime.
Final Conclusion: Governance Mechanisms for Socially Sustainable Urban Densification
Authors: Debrunner Gabriela
Published: December 2023

The results of this book extend the knowledge about why some groups or interests experience disproportional access to housing stocks in densifying urban areas, and tend to lose while others tend to win. In the concluding part, the key results answering the three sub-questions (SQ1 to SQ3) are presented. Results are discussed that contribute to neoinstitutionalist political ecology research. Chapter 6 and this chapter close with the findings that answer the main research question (RQ) and rich conclusions supporting the point of this book, i.e. that densification has become a business, which creates exclusion and marginalization for some part of the urban population. Although results are limited to Switzerland, potential for generalization to other states and urban contexts results from the identified key results and causal mechanisms. Finally, the limitations of the theoretical and methodological model applied are discussed (Sect. 7.2), and an outlook for future research is presented (Sect. 7.3).
Standardisierte Erhebungsinstrumente
Authors: Thimm Antonia , Dieckmann Friedrich
Published: January 2024

Die Anwendung standardisierter Erhebungsinstrumente ist in der empirischen Forschung zum Wohnen von Menschen mit intellektueller Beeinträchtigung in Deutschland weniger verbreitet als in anderen Ländern. In diesem Kapitel werden international gebräuchliche Erhebungsinstrumente für die vier Themenbereiche „adaptives Verhalten“, „Selbstbestimmung“, „Teilhabe im Sozialraum“ und „Qualität von Assistenzleistungen“ vorgestellt. Adaptives Verhalten ist für die Beschreibung des Personenkreises von Menschen mit intellektueller Beeinträchtigung ein bedeutsames Konstrukt und im Zusammenspiel mit anderen Bedingungen ein wichtiger Einflussfaktor für die Teilhabechancen und Lebensqualität von Menschen mit intellektueller Beeinträchtigung. Selbstbestimmung und Teilhabe im Sozialraum sind zwei Kerndimensionen des Lebensqualitätskonzepts von Schalock R, & Verdugo M (Handbook on quality of life for human service practitioners. American Association on Mental Retardation, 2002) und wichtige Leitziele für die Unterstützung der Lebensführung von Menschen mit intellektueller Beeinträchtigung. Die Qualität der Assistenzleistungen beeinflusst die Lebensqualität von Menschen mit Beeinträchtigung. Vorgestellt werden strukturierte Beobachtungsinstrumente, mit denen sich die Assistenzleistungen überprüfen lassen. Die Autor*innen machen auf international verbreitete Messinstrumente aufmerksam, deren Übersetzung, Anwendung und Weiterentwicklung lohnenswert wäre. Mit deutschsprachigen Versionen bewährter Instrumente können Forschungsergebnisse aus dem deutschsprachigen Raum besser in internationale Diskurse eingebracht werden. Die Instrumente lassen sich darüber hinaus auch für Zwecke in der Praxis nutzen.
Partizipative Forschung
Authors: Schuppener Saskia
Published: January 2024

Der Beitrag befasst sich mit verschiedenen Relevanzsetzungen und Diskussionsaspekten Partizipativer Forschung. Ausgehend von forschungsethischen Fragen werden die Ansprüche der Subjektorientierung und der Pluralisierung im Rahmen Partizipativer Forschungsformate reflektiert. Hier werden Fragen der Ausgestaltungsmacht und Wirkung von Forschung beleuchtet und auf der Basis eines Anspruchs von Perspektivenvielfalt gedeutet. Folgend werden unterschiedliche Ansätze und Qualitätskriterien Partizipativer Forschung skizziert und vor dem Hintergrund eines hegemonieselbstkritischen Zugangs im Hochschulsektor kritisch hinterfragt. Den Abschluss bildet ein Einblick in eine partizipativ-orientierte Forschungsarbeit mit Jugendlichen mit zugeschriebener geistiger Behinderung. Diese Forschungszusammenarbeit zu dem sensiblen Thema ,Autonomieeinschränkungen und freiheitsentziehende Maßnahmen‘ wird hier entlang der zuvor aufgezeigten forschungsethischen Spannungsfelder (selbst)kritisch diskutiert.