brainlife.io: a decentralized and open-source cloud platform to support neuroscience research.

Neuroscience is advancing standardization and tool development to support rigor and transparency. Consequently, data pipeline complexity has increased, hindering FAIR (findable, accessible, interoperable and reusable) access. brainlife.io was developed to democratize neuroimaging research. The platform provides data standardization, management, visualization and processing and automatically tracks the provenance history of thousands of data objects. Here, brainlife.io is described and evaluated for validity, reliability, reproducibility, replicability and scientific utility using four data modalities and 3,200 participants.

Neoadjuvant short-course radiotherapy followed by camrelizumab and chemotherapy in locally advanced rectal cancer (UNION): early outcomes of a multicenter randomized phase III trial.

BACKGROUND: Neoadjuvant short-course radiotherapy (SCRT) followed by CAPOX and camrelizumab (a programmed cell death protein 1 monoclonal antibody) has shown potential clinical activity for locally advanced rectal cancer (LARC) in a phase II trial. This study aimed to further confirm the efficacy and safety of SCRT followed by CAPOX and camrelizumab compared to long-course chemoradiotherapy (LCRT) followed by CAPOX alone as neoadjuvant treatment for LARC. PATIENTS AND METHODS: In this randomized, phase III trial, patients with T3-4/N+ rectal adenocarcinoma were randomly assigned (1 : 1) to receive SCRT or long-course chemoradiotherapy (LCRT), followed by two cycles of camrelizumab and CAPOX or CAPOX alone, respectively. After surgery, each arm underwent either six cycles of camrelizumab and CAPOX, followed by up to 17 doses of camrelizumab, or six cycles of CAPOX. The primary endpoint was pathological complete response (pCR) rate (ypT0N0) assessed by a blinded independent review committee. Key secondary endpoints tested hierarchically were 3-year event-free survival (EFS) rate and overall survival (OS). RESULTS: Between July 2021 and March 2023, the intention-to-treat population comprised 113 patients in the experimental arm and 118 patients in the control arm, with surgery carried out in 92% and 83.9%, respectively. At data cut-off (11 July 2023), the pCR rates were 39.8% [95% confidence interval (CI) 30.7% to 49.5%] in the experimental arm compared to 15.3% (95% CI 9.3% to 23.0%) in the control arm (difference, 24.6%; odds ratio, 3.7; 95% CI 2.0-6.9; P < 0.001). In each arm, surgical complication rates were 40.0% and 40.8%, and grade ≥3 treatment-related adverse events were 29.2% and 27.2%. Three-year EFS rate and OS continue to mature. CONCLUSIONS: In LARC patients, neoadjuvant SCRT followed by camrelizumab plus CAPOX demonstrated a significantly higher pCR rate than LCRT followed by CAPOX, with a well-tolerated safety profile. SCRT followed by camrelizumab and chemotherapy can be recommended as a neoadjuvant treatment modality for these patients.

Early life supplementation with mannan-rich fraction to regulate rumen microbiota, gut health, immunity and growth performance in dairy goat kids.

Enhancing gastrointestinal health, immunity, and digestion are key factors to support dairy goat kid performance. Several additives have been studied in relation to these actions. This study investigated the impact of mannan-rich fraction (MRF) inclusion in goat milk on the growth performance, gut health, rumen fermentation and microbial profiles of Xinong Saanen dairy goat kids. Eighty kids aged 14 d and 4.72 ± 0.33 kg body weight (BW) were randomly assigned into 2 groups: Control and MRF (1g/d MRF mixed into milk), each group consisted of 40 kids with 10 kids per pen. All kids were given milk individually and fed starter diet by pen, with the trial lasting 10 weeks. BW and blood samples were collected on the 7th day at 2, 6, 10 and 12 weeks of age, and feed intake was determined daily. From the 1st to 7th day at 12 weeks of age, fecal samples were collected on 4 kids from each group to analyze nutrient digestibility. On the 7th day of 12 weeks of age, 4 kids from each group were slaughtered for evaluation of rumen fermentation, rumen microbiota and gut morphology. The results indicated that MRF supplementation led to greater overall BW (P < 0.01), overall starter dry matter intake (DMI) (P < 0.01) and overall average daily gain (ADG) (P = 0.021), while showing lower overall diarrhea rate (P < 0.01). However, no difference in overall feed efficiency (FE) (P = 0.063) and apparent digestibility of nutrients was observed (P > 0.05). Furthermore, MRF supplementation resulted in increased ileal villus height (P = 0.05), and higher RNA expression of Claudin-1 and Occuldin in the duodenum (P < 0.05), ZO-1, JAM-2, and Occuldin in the jejunum (P < 0.05), and Claudin-1, JAM-2, and Occuldin in the ileum (P < 0.05). Additionally, the concentrations of overall IgA, overall IgM and overall IgG were higher in the MRF group (P < 0.01). The concentrations of ruminal acetate and total volatile fatty acid (TVFA) were higher with MRF supplementation (P < 0.05). Meanwhile, supplementation with MRF resulted in higher abundance of Bacteroidetes and Succinivibrio, but lower abundance of Firmicutes and Succiniclasticum in the rumen. In conclusion, growth performance, gut health, immunity, and ruminal microbial structure of dairy goat kids benefited from MRF supplementation.

[Surgical treatment and prognosis analysis of hilar cholangiocarcinoma].

Objective: To investigate the surgical treatment effect and prognostic factors of hilar cholangiocarcinoma. Methods: This is an ambispective cohort study. From August 2005 to December 2022,data of 510 patients who diagnosed with hilar cholangiocarcinoma and underwent surgical resection at the Hepatobiliary Center of the First Affiliated Hospital of Nanjing Medical University were retrospectively collected. In the cohort,there were 324 males and 186 females,with an age of (M (IQR)) 63(13)years (range:25 to 85 years). The liver function at admission was Child-Pugh A (343 cases,67.3%) and Child-Pugh B (167 cases,32.7%). Three hundred and seventy-two(72.9%) patients had jaundice symptoms and the median total bilirubin was 126.3(197.6) µmol/L(range: 5.4 to 722.8 µmol/L) at admission. Two hundred and fourty-seven cases (48.4%) were treated with percutaneous transhepatic cholangial drainage or endoscopic nasobiliary drainage before operation. The median bilirubin level in the drainage group decreased from 186.4 µmol/L to 85.5 µmol/L before operation. Multivariate Logistic regression was used to identify the influencing factors for R0 resection,and Cox regression was used to construct multivariate prediction models for overall survival(OS) and disease-free survival(DFS). Results: Among 510 patients who underwent surgical resection,Bismuth-Corlett type Ⅲ-Ⅳ patients accounted for 71.8%,among which 86.1% (315/366) underwent hemi-hepatectomy,while 81.9% (118/144) underwent extrahepatic biliary duct resection alone in Bismuch-Corlett type Ⅰ-Ⅱ patients. The median OS time was 22.8 months, and the OS rates at 1-,3-,5-and 10-year were 72.2%,35.6%,24.8% and 11.0%,respectively. The median DFS time was 15.2 months,and the DFS rates was 66.0%,32.4%,20.9% and 11.0%,respectively. The R0 resection rate was 64.5% (329/510), and the OS rates of patients with R0 resection at 1-,3-,5-and 10-year were 82.5%, 48.6%, 34.4%, 15.2%,respectively. The morbidity of Clavien-Dindo grade Ⅲ-Ⅴ complications was 26.1%(133/510) and the 30-day mortality was 4.3% (22/510). Multivariate Logistic regression indicated that Bismuth-Corlett type Ⅰ-Ⅲ (P=0.009), hemi-hepatectomy and extended resection (P=0.001),T1 and T2 patients without vascular invasion (T2 vs. T1:OR=1.43 (0.61-3.35),P=0.413;T3 vs. T1:OR=2.57 (1.03-6.41), P=0.010;T4 vs. T1, OR=3.77 (1.37-10.38), P<0.01) were more likely to obtain R0 resection. Preoperative bilirubin,Child-Pugh grade,tumor size,surgical margin,T stage,N stage,nerve infiltration and Edmondson grade were independent prognostic factors for OS and DFS of hilar cholangiocarcinoma patients without distant metastasis. Conclusions: Radical surgical resection is necessary to prolong the long-term survival of hilar cholangiocarcinoma patients. Hemi-hepatectomy and extended resection,regional lymph node dissection and combined vascular resection if necessary,can improve R0 resection rate.

[Preparation of chitin/hyaluronic acid/collagen hydrogel loaded with mouse adipose-derived stem cells and its effects on wound healing of full-thickness skin defects in rats].

Objective: To prepare the chitin/hyaluronic acid/collagen hydrogel loaded with mouse adipose-derived stem cells and to explore its effects on wound healing of full-thickness skin defects in rats. Methods: The research was an experimental research. Chitin nanofibers were prepared by acid hydrolysis and alkaline extraction method, and then mixed with hyaluronic acid and collagen to prepare chitin/hyaluronic acid/collagen hydrogels (hereinafter referred to as hydrogels). Besides, the hydrogels loaded with mouse adipose-derived stem cells were prepared. Thirty male 12-week-old guinea pigs were divided into negative control group, positive control group, and hydrogel group according to the random number table, with 10 guinea pigs in each group. Ethanol, 4-aminobenzoic acid ethyl ester, or the aforementioned prepared hydrogels without cells were topically applied on both sides of back of guinea pigs respectively for induced contact and stimulated contact, and skin edema and erythema formation were observed at 24 and 48 h after stimulated contact. Adipose-derived stem cells from mice were divided into normal control group cultured routinely and hydrogel group cultured with the aforementioned prepared hydrogels without cells. After 3 d of culture, protein expressions of platelet-derived growth factor-D (PDGF-D), insulin-like growth factor-Ⅰ (IGF-Ⅰ), and transforming growth factor ß1 (TGF-ß1) were detected by Western blotting (n=3). Eight male 8-week-old Sprague-Dawley rats were taken and a circular full-thickness skin defect wound was created on each side of the back. The wounds were divided into blank control group without any treatment and hydrogel group with the aforementioned prepared hydrogels loaded with adipose-derived stem cells applied. Wound healing was observed at 0 (immediately), 2, 4, 8, and 10 d after injury, and the wound healing rate was calculated at 2, 4, 8, and 10 d after injury. Wound tissue samples at 10 d after injury were collected, the new tissue formation was observed by hematoxylin-eosin staining; the concentrations of interleukin-1α (IL-1α), IL-6, IL-4, and IL-10 were detected by enzyme-linked immunosorbent assay method; the expressions of CD16 and CD206 positive cells were observed by immunohistochemical staining and the percentages of positive cells were calculated. The sample numbers in animal experiment were all 8. Results: At 24 h after stimulated contact, no skin edema was observed in the three groups of guinea pigs, and only mild skin erythema was observed in 7 guinea pigs in positive control group. At 48 h after stimulated contact, skin erythema was observed in 8 guinea pigs and skin edema was observed in 4 guinea pigs in positive control group, while no obvious skin erythema or edema was observed in guinea pigs in the other two groups. After 3 d of culture, the protein expression levels of PDGF-D, IGF-I, and TGF-ß1 in adipose-derived stem cells in hydrogel group were significantly higher than those in normal control group (with t values of 12.91, 11.83, and 7.92, respectively, P<0.05). From 0 to 10 d after injury, the wound areas in both groups gradually decreased, and the wounds in hydrogel group were almost completely healed at 10 d after injury. At 4, 8, and 10 d after injury, the wound healing rates in hydrogel group were (38±4)%, (54±5)%, and (69±6)%, respectively, which were significantly higher than (21±6)%, (29±7)%, and (31±7)% in blank control group (with t values of 3.82, 3.97, and 4.05, respectively, Pvalues all <0.05). At 10 d after injury, compared with those in blank control group, the epidermis in wound in hydrogel group was more intact, and there were increases in hair follicles, blood vessels, and other skin appendages. At 10 d after injury, the concentrations of IL-1α and IL-6 in wound tissue in hydrogel group were significantly lower than those in blank control group (with tvalues of 8.21 and 7.99, respectively, P<0.05), while the concentrations of IL-4 and IL-10 were significantly higher than those in blank control group (with tvalues of 6.57 and 9.03, respectively, P<0.05). The percentage of CD16 positive cells in wound tissue in hydrogel group was significantly lower than that in blank control group (t=8.02, P<0.05), while the percentage of CD206 positive cells was significantly higher than that in blank control group (t=7.21, P<0.05). Conclusions: The hydrogel loaded with mouse adipose-derived stem cells is non-allergenic, can promote the secretion of growth factors in adipose-derived stem cells, promote the polarization of macrophages to M2 phenotype in wound tissue in rats with full-thickness skin defects, and alleviate inflammatory reaction, thereby promoting wound healing.

[The principle and practice of vidian neurectomy].

The latest research findings on bidirectional regulation of neuro-immunity through traditional neural circuits shed new light on the theoretical basis of the role of vidian neurectomy (VN). This article aims to provide a comprehensive understanding of VN, including the history of VN, the principle of neuroimmuno-interaction, the applied anatomy of VN as well as the methods of transnasal endoscopic surgery. Additionally, we introduce the concept of the nose-brain axis, which was proposed based on the advancement in the area of neuro-immune interactions.

The Effect of Thymosin Alpha 1 on Severe Acute Pancreatitis in Rats / Estudios sobre el efecto de la timosina alfa 1 sobre la pancreatitis aguda grave en ratas

ABSTRACT Objective: To observe the effect of thymosin alpha l (Tα1) on severe acute pancreatitis (SAP) in rats. Methods: Twenty-four adult male Sprague-Dawley rats were randomly divided into three groups (eight in each group): control group (Group A), SAP group (Group B) and Tα1 treatment group (Group C). Animal models of SAP were made by retrograde injection of 5% sodium taurocholate into the biliopancreatic duct. Rats in Group C were treated with Tα1 (6 mg/kg) via intraperitoneal administration prior to SAP modelling. Eight rats in each group were sacrificed at 12 hours, respectively, after modelling. The serum levels of amylase, tumour necrosis factor-α (TNF-α), interleukin-lβ (IL-lβ and interleukin-6 (IL-6) were detected in each group. The pathological scores of the tissue in the pancreas head were observed by light microscopy. Results: The levels of serum amylase of Group B were 6378 ± 538 U/L, which were significantly higher than those (4587 ± 478 U/L) of Group C (p < 0.05). The levels of serum TNF-α of Group B were 360.32 ± 28.67 pg/mL, which were higher than those (269.99 ± 26.11 pg/mL) of Group C (p < 0.05). The levels of serum IL-lβ of Group B were 435.93 ± 36.00 pg/mL, which were higher than those (312.42 ± 17.89 pg/mL) of Group C (p < 0.05). The levels of serum IL-6 of Group B were 433.90 ± 28.36 pg/mL, which were higher than those (289.98 ± 23.00 pg/mL) of Group C (p < 0.05). The pancreatic pathological scores of Group B were 13.34 ± 2.19, which were higher than those (6.39 ± 1.86) of Group C (p < 0.05). Conclusion: Thymosin alpha 1 could decrease proinflammatory cytokines and reduce pancreas injury and had a protective effect in rats with SAP. This provides a new strategy for the clinical treatment of SAP.

RESUMEN Objetivo: Observar el efecto de la timosina alfa l (Tα1) sobre la pancreatitis aguda grave (PAG) en ratas. Métodos: Veinticuatro ratas Sprague-Dawley adultas machos fueron divididas aleatoriamente en tres grupos (ocho en cada grupo): grupo de control (grupo A), grupo de PAG (grupo B) y grupo de tratamiento con Tα1 (grupo C). Los modelos animales de PAG fueron creados mediante inyección retrógrada de taurocolato de sodio al 5% en el conducto biliopancreático. Las ratas del grupo C se trataron con Tα1 (6 mg/kg) via administración intraperitoneal antes del modelado de PAG. Las ocho ratas en cada grupo fueron sacrificadas a las 12 horas, respectivamente, después del modelado. Los niveles séricos de amilasa, factor-α de necrosis tumoral (TNF-α), interleucina-β (Il-β) e interleucina-6 (IL-6) fueron detectados en cada grupo. Las puntuaciones patológicas del tejido en la cabeza del páncreas fueron observadas mediante microscopía de luz. Resultados: Los niveles de amilasa sérica del grupo B fueron 6378 ± 538 U/L, y resultaron significativamente más altos (p < 0.05) que los niveles 4587 ± 478 U/L del grupo C. Los niveles séricos de TNF-α del grupo B fueron 360.32 ± 28.67 pg/mL, y resultaron ser más altos (p < 0.05) que los 269.99 ± 26.11 pg/mL del grupo C. Los niveles séricos de Il-β del grupo B fueron 435.93 ± 36.00 pg/mL, y fueron más altos (p < 0.05) que los 312.42 ± 17.89 pg/mL) del grupo C. Los niveles de suero IL-6 del grupo B fueron 433.90 ± 28.36 pg/mL, y resultaron ser más altos (p < 0.05) que los 289.98 ± 23.00 pg/mL del grupo C. Las puntuaciones patológicas pancreáticas del grupo B fueron 13.34 ± 2.19, y resultaron ser más altas (p < 0.05) que las puntuaciones 6.39 ± 1.86 del grupo C. Conclusión: La timosina alfa pudo disminuir las citoquinas proinflamatorias y reducir la lesión del páncreas, y tuvo un efecto protector en las ratas con PAG. Esto ofrece una nueva estrategia para el tratamiento clínico de PAG.