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Intussusception is a common pediatric emergency that causes significant morbidity and mortality, particularly in low- to middle-income countries. The laparoscopic management of intussusception following failed non-invasive methods remains a topic of debate. This study aims to evaluate the long-term outcomes of minimally invasive approaches for intussusception. A retrospective analysis was conducted on patients who underwent minimally invasive surgery for intussusception between January 2016 and December 2020 at our institution. Data on patient demographics, pre-operative and intra-operative variables, immediate postoperative complications, length of hospital stay, and long-term results were collected. A total of 181 patients underwent minimally invasive surgery, including 117 boys (64.6%) and 64 girls (35.4%), with a median age of 8 months (range: 2-134). The median hospital stay was 4 days. Thirty-nine patients underwent trans-umbilical mini-open reduction (MO group), while 142 had laparoscopic exploration after failed air enema reduction. Among them, 40 had successful laparoscopic reduction (LAP group), and 102 required conversion to laparoscopic-assisted mini-open reduction (LAMO group). No intra-operative or immediate postoperative complications were observed. Recurrence occurred in 13 patients (7.2%) after a median follow-up of 43 months, with 6 patients (3.3%) requiring laparoscopic adhesiolysis due to bowel adhesions. In conclusion, minimally invasive surgery for intussusception is a safe and feasible approach with excellent long-term outcomes., Competing Interests: Declarations. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)

Glioma cells hijack developmental programs to control cell state. Here, we uncover a glioma cell state-specific metabolic liability that can be therapeutically targeted. To model cell conditions at brain tumor inception, we generated genetically engineered murine gliomas, with deletion of p53 alone (p53) or with constitutively active Notch signaling (N1IC), a pathway critical in controlling astrocyte differentiation during brain development. N1IC tumors harbored quiescent astrocyte-like transformed cell populations while p53 tumors were predominantly comprised of proliferating progenitor-like cell states. Further, N1IC transformed cells exhibited increased mitochondrial lipid peroxidation, high ROS production and depletion of reduced glutathione. This altered mitochondrial phenotype rendered the astrocyte-like, quiescent populations more sensitive to pharmacologic or genetic inhibition of the lipid hydroperoxidase GPX4 and induction of ferroptosis. Treatment of patient-derived early-passage cell lines and glioma slice cultures generated from surgical samples with a GPX4 inhibitor induced selective depletion of quiescent astrocyte-like glioma cell populations with similar metabolic profiles. Collectively, these findings reveal a specific therapeutic vulnerability to ferroptosis linked to mitochondrial redox imbalance in a subpopulation of quiescent astrocyte-like glioma cells resistant to standard forms of treatment., (© 2024. The Author(s).)

The mechanistic target of rapamycin (mTOR) is a kinase whose activation is associated with poor prognosis in pre-B cell acute lymphoblastic leukemia (B-ALL). These and other findings have prompted diverse strategies for targeting mTOR signaling in B-ALL and other B-cell malignancies. In cellular models of Philadelphia Chromosome-positive (Ph+) B-ALL, mTOR kinase inhibitors (TOR-KIs) that inhibit both mTOR-complex-1 (mTORC1) and mTOR-complex-2 (mTORC2) enhance the cytotoxicity of tyrosine kinase inhibitors (TKIs) such as dasatinib. However, TOR-KIs have not shown substantial efficacy at tolerated doses in blood cancer clinical trials. Selective inhibition of mTORC1 or downstream effectors provides alternative strategies that may improve selectivity towards leukemia cells. Of particular interest is the eukaryotic initiation factor 4F (eIF4F) complex that mediates cap-dependent translation. Here we use novel chemical and genetic approaches to show that selective targeting of either mTORC1 kinase activity or components of the eIF4F complex sensitizes murine BCR-ABL-dependent pre-B leukemia cells to dasatinib. SBI-756, a small molecule inhibitor of eIF4F assembly, sensitizes human Ph+ and Ph-like B-ALL cells to dasatinib cytotoxicity without affecting survival of T lymphocytes or natural killer cells. These findings support the further evaluation of eIF4F-targeted molecules in combination therapies with TKIs in B-ALL and other blood cancers., (© 2021. The Author(s).)

In this article, we investigated the efficiency of a magnetic resonant wireless power transfer (MR-WPT) in conducting medium and found out an optimal frequency for designing the system. In conducting environment, the eddy current loss is generated by the high-frequency alternating currents in the coils. It is manifested by increased radiation resistance of resonator coil leads to decrease the quality factor (Q-factor), which reduces the wireless power transfer (WPT) efficiency in conducting medium. The Q-factor of the resonator coil strongly depending on the conductivity, frequency, and thickness of conducting block. Two MR-WPT systems operating at 10.0 MHz and 20.0 MHz are implemented to study the effect of conducting medium on efficiency. The achieved results indicated that the 20.0 MHz system has higher efficiency at a conductivity smaller than 6.0 S/m. However, at the larger conductivity, the 10.0 MHz system is more efficient. The results provide a method to determine the optimal frequency of a WPT system operating in the conducting medium with various conductivities and thickness blocks. This method can be used to design MR-WPT systems in numerous situations, such as autonomous underwater vehicles and medical implants., (© 2021. The Author(s).)

Despite the importance of urban trees' surface temperature in assessing micro-climate interactions between trees and the surrounding environment, their diurnal evolution has been largely understudied at a city-wide scale due to a lack of effective thermal observations. By downscaling ECOSTRESS land surface temperature imaginary over New York City, we provide the first diurnal analysis of city-scale canopy temperature. Research reveals a remarkable spatial variation of the canopy temperature during daytime up to 5.6 K (standard deviation, STD), while the nighttime STD remains low at 1.7 K. Further, our analysis shows that the greenspace coverage and distance to bluespaces play an important role in cooling the local canopy during daytime, explaining 25.0-41.1% of daytime spatial variation of canopy temperatures while surrounding buildings modulate canopy temperature asymmetrically diurnally: reduced daytime warming and reduced nocturnal cooling. Built on space-borne observations and a flexible yet robust statistical method, our research design can be easily transferable to explore urban trees' response to local climate across cities, highlighting the potentials of advancing the science and technologies for urban forest management.

We successfully demonstrated a detailed and systematic enhancement of organic field effect transistors (OFETs) performance using dithienothiophene (DTT) and furan-flanked diketopyrrolopyrrole based donor-acceptor conjugated polymer semiconductor namely PDPPF-DTT as an active semiconductor. The self-assembled monolayers (SAMs) treatments at interface junctions of the semiconductor-dielectric and at the semiconductor-metal electrodes has been implemented using bottom gate bottom contact device geometry. Due to SAM treatment at the interface using tailored approach, the significant reduction of threshold voltage (V th ) from - 15.42 to + 5.74 V has been observed. In addition to tuning effect of V th , simultaneously charge carrier mobility (µ FET ) has been also enhanced the from 9.94 × 10 -4 cm 2 /Vs to 0.18 cm 2 /Vs. In order to calculate the trap density in each OFET device, the hysteresis in transfer characteristics has been studied in detail for bare and SAM treated devices. Higher trap density in Penta-fluoro-benzene-thiol (PFBT) treated OFET devices enhances the gate field, which in turn controls the charge carrier density in the channel, and hence gives lower V th  = + 5.74 V. Also, PFBT treatment enhances the trapped interface electrons, which helps to enhance the mobility in this OFET architecture. The overall effect has led to possibility of reduction in the V th with simultaneous enhancements of µ FET in OFETs, following systematic device engineering methodology.

The spectral properties of Fano resonance generated in multilayer dielectric gratings (MDGs) are reported and numerically investigated in this paper. We examine the MDG consisting of numerous identically alternative chalcogenide glass (As 2 S 3 ) and silica (SiO 2 ) multilayers with several grating widths inscribed through the structure, emphasizing quality (Q) and asymmetric (q) factors. Manipulation of Fano lineshape and its linear characteristics can be achieved by tailoring the layers' amount and grating widths so that the proposed structure can be applicable for several optical applications. Moreover, we demonstrate the switching/bistability behaviors of the MDG at Fano resonance which provide a significant switching intensity reduction compared to the established Lorentzian resonant structures.

This study presents a description of an open database on scientific output of Vietnamese researchers in social sciences and humanities, one that corrects for the shortcomings in current research publication databases such as data duplication, slow update, and a substantial cost of doing science. Here, using scientists' self-reports, open online sources and cross-checking with Scopus database, we introduce a manual system and its semi-automated version of the database on the profiles of 657 Vietnamese researchers in social sciences and humanities who have published in Scopus-indexed journals from 2008 to 2018. The final system also records 973 foreign co-authors, 1,289 papers, and 789 affiliations. The data collection method, highly applicable for other sources, could be replicated in other developing countries while its content be used in cross-section, multivariate, and network data analyses. The open database is expected to help Vietnam revamp its research capacity and meet the public demand for greater transparency in science management.

Human fibroblast growth factor 21 (hFGF21) has been characterized as an important regulator of glucose and lipid metabolism homeostasis. Here, to produce hFGF21 efficiently in Escherichia coli, the expression and solubility of hFGF21 were tested and optimised by fusing the protein with one of eight tags: hexahistidine (His6), thioredoxin (Trx), small ubiquitin-related modifier (Sumo), glutathione S-transferase (GST), maltose-binding protein (MBP), N-utilisation substance protein A (NusA), human protein disulphide isomerase (PDI), and the b'a' domain of PDI (PDIb'a'). Each tag increased solubility of the protein when the expression temperature was 18°C. Unlike many other tags that were tested, MBP significantly enhanced the solubility of the protein also in the culture condition at 37°C. Thus, the MBP-hFGF21 construct was further pursued for optimisation of affinity chromatography purification. After tag removal, 8.1 mg of pure hFGF21 was obtained as a final product from 500 mL of starting culture. The protein was then characterised by mass spectroscopy and an in vitro functional assay using NIH-3T3 cells transfected with a β-klotho reporter gene. These characteristics are similar to those of commercial hFGF21. Thus, the MBP tag is useful for efficient prokaryotic production and purification of bioactive hFGF21.

The type VI secretion system (T6SS) is a multiprotein machine widespread in Gram-negative bacteria that delivers toxins into both eukaryotic and prokaryotic cells. The mechanism of action of the T6SS is comparable to that of contractile myophages. The T6SS builds a tail-like structure made of an inner tube wrapped by a sheath, assembled under an extended conformation. Contraction of the sheath propels the inner tube towards the target cell. The T6SS tail is assembled on a platform-the baseplate-which is functionally similar to bacteriophage baseplates. In addition, the baseplate docks the tail to a trans-envelope membrane complex that orients the tail towards the target. Here, we report the crystal structure of TssK, a central component of the T6SS baseplate. We show that TssK is composed of three domains, and establish the contribution of each domain to the interaction with TssK partners. Importantly, this study reveals that the N-terminal domain of TssK is structurally homologous to the shoulder domain of phage receptor-binding proteins, and the C-terminal domain binds the membrane complex. We propose that TssK has conserved the domain of attachment to the virion particle but has evolved the reception domain to use the T6SS membrane complex as receptor.

Contemporary chemotherapeutic treatments incorporate the use of several agents in combination. However, selecting the most appropriate drugs for such therapy is not necessarily an easy or straightforward task. Here, we describe a targeted approach that can facilitate the reliable selection of chemotherapeutic drug combinations through the interrogation of drug-resistance gene networks. Our method employed single-cell eukaryote fission yeast (Schizosaccharomyces pombe) as a model of proliferating cells to delineate a drug resistance gene network using a synthetic lethality workflow. Using the results of a previous unbiased screen, we assessed the genetic overlap of doxorubicin with six other drugs harboring varied mechanisms of action. Using this fission yeast model, drug-specific ontological sub-classifications were identified through the computation of relative hypersensitivities. We found that human gastric adenocarcinoma cells can be sensitized to doxorubicin by concomitant treatment with cisplatin, an intra-DNA strand crosslinking agent, and suberoylanilide hydroxamic acid, a histone deacetylase inhibitor. Our findings point to the utility of fission yeast as a model and the differential targeting of a conserved gene interaction network when screening for successful chemotherapeutic drug combinations for human cells.

Doxorubicin, a chemotherapeutic agent, inhibits the religation step of topoisomerase II (Top2). However, the downstream ramifications of this action are unknown. Here we performed epistasis analyses of top2 with 63 genes representing doxorubicin resistance (DXR) genes in fission yeast and revealed a subset that synergistically collaborate with Top2 to confer DXR. Our findings show that the chromatin-regulating RSC and SAGA complexes act with Top2 in a cluster that is functionally distinct from the Ino80 complex. In various DXR mutants, doxorubicin hypersensitivity was unexpectedly suppressed by a concomitant top2 mutation. Several DXR proteins showed centromeric localization, and their disruption resulted in centromeric defects and chromosome missegregation. An additional top2 mutation could restore centromeric chromatin integrity, suggesting a counterbalance between Top2 and these DXR factors in conferring doxorubicin resistance. Overall, this molecular basis for mitotic catastrophe associated with doxorubicin treatment will help to facilitate drug combinatorial usage in doxorubicin-related chemotherapeutic regimens.

Several linkage analyses implicated the chromosome 9q22 region in attention deficit/hyperactivity disorder (ADHD), a neurodevelopmental disease with remarkable persistence into adulthood. This locus contains the brain-expressed GTP-binding RAS-like 2 gene (DIRAS2) thought to regulate neurogenesis. As DIRAS2 is a positional and functional ADHD candidate gene, we conducted an association study in 600 patients suffering from adult ADHD (aADHD) and 420 controls. Replication samples consisted of 1035 aADHD patients and 1381 controls, as well as 166 families with a child affected from childhood ADHD. Given the high degree of co-morbidity with ADHD, we also investigated patients suffering from bipolar disorder (BD) (n=336) or personality disorders (PDs) (n=622). Twelve single-nucleotide polymorphisms (SNPs) covering the structural gene and the transcriptional control region of DIRAS2 were analyzed. Four SNPs and two haplotype blocks showed evidence of association with ADHD, with nominal p-values ranging from p=0.006 to p=0.05. In the adult replication samples, we obtained a consistent effect of rs1412005 and of a risk haplotype containing the promoter region (p=0.026). Meta-analysis resulted in a significant common OR of 1.12 (p=0.04) for rs1412005 and confirmed association with the promoter risk haplotype (OR=1.45, p=0.0003). Subsequent analysis in nuclear families with childhood ADHD again showed an association of the promoter haplotype block (p=0.02). rs1412005 also increased risk toward BD (p=0.026) and cluster B PD (p=0.031). Additional SNPs showed association with personality scores (p=0.008-0.048). Converging lines of evidence implicate genetic variance in the promoter region of DIRAS2 in the etiology of ADHD and co-morbid impulsive disorders.

Recently, several genome-wide association studies (GWAS) on bipolar disorder (BPD) suggested novel risk genes. However, only few of them were followed up and further, the specificity of these genes is even more elusive. To address these issues, we genotyped SNPs in ANK3, CACNA1C, CMTM8, DGKH, EGFR, and NPAS3, which were significantly associated with BPD in previous GWAS, in a sample of 380 BPD patients. Replicated SNPs were then followed up in patients suffering from unipolar depression (UPD; n=387) or adult attention-deficit/hyperactivity disorder (aADHD; n=535). While we could not confirm an association of ANK3, CACNA1C, and EGFR with BPD, 10 SNPs in DGKH, CMTM8, and NPAS3 were nominally associated with disease, with two DGKH markers surviving correction for multiple testing. When these were followed up in UPD and aADHD, seven DGKH SNPs were also associated with UPD, while one SNP each in NPAS3 and CMTM8 and four in DGKH were linked to aADHD. Furthermore, a DGKH haplotype consisting of rs994856/rs9525580/rs9525584 GAT was associated with all disorders tested, while the complementary AGC haplotype was protective. The corresponding haploblock spans a 27-kb region covering exons coding for amino acids 65-243, and thus might include functional variants yet to be identified. We demonstrate an association of DGKH with BPD, UPD, and aADHD by applying a two-stage design. These disorders share the feature of mood instability, so that this phenotype might be associated with genetic variation in DGKH.

DLK1 is part of the Notch signalling pathway that controls various developmental processes. A functional role for DLK1 in adipogenesis is suggested by several animal models. Interestingly, the DLK1 gene is imprinted in eutherian mammals. To study whether variations in DLK1 affect body weight in humans, we analysed 32 polymorphisms in a 109 kb genomic region encompassing DLK1 on human chromosome 14. In a study sample of 1025 French and German trio families comprised of both parents and extremely obese offspring we found a single nucleotide polymorphism (rs1802710) associated with child and adolescent obesity. Analysis of the allelic transmission pattern indicated the existence of polar overdominance, an unusual mode of non-Mendelian inheritance in humans previously known from the callipyge mutation in sheep.