tbuckley/cabot-search huggingface dataset:
SAIL66, a next generation CLDN6-targeting T-cell engager, demonstrates potent antitumor efficacy through dual binding to CD3/CD137
Authors: Takayuki Kamikawa, Naoki Kimura, Shinya Ishii, Masaru Muraoka, Tatsushi Kodama, Kenji Taniguchi, Moe Yoshimoto, Momoko Miura-Okuda, Ryo Uchikawa, Chie Kato, Junko Shinozuka, Sho Akai, Sotaro Naoi, Nanami Tomioka, Nishiki Nagaya, Chai Ling Pang, Gupta Garvita, Shu Feng, Mei Shimada, Mika Kamata-Sakurai, Hiroyuki Aburatani, Takehisa Kitazawa, Tomoyuki Igawa
Journal: Journal for ImmunoTherapy of Cancer (2024)

Ovarian cancer remains a formidable challenge in oncology, necessitating innovative therapeutic approaches. Claudin-6 (CLDN6), a member of the tight junction molecule CLDN family, exhibits negligible expression in healthy tissues but displays aberrant upregulation in various malignancies, including ovarian cancer. Although several therapeutic modalities targeting CLDN6 are currently under investigation, there is still a need for more potent therapeutic options. While T-cell engagers (TCEs) hold substantial promise as potent immunotherapeutic agents, their current efficacy and safety in terms of target antigen selection and T-cell exhaustion due to only CD3 stimulation without co-stimulation must be improved, particularly against solid tumors. To provide an efficacious treatment option for ovarian cancer, we generated SAIL66, a tri-specific antibody against CLDN6/CD3/CD137.
Innovative techniques using a novel thin scope for stent placement in malignant colonic obstruction with severe angulation deformity
Authors: Yosei Sawai, Tomohiro Shimada, Taku Yamagata, Yoshihide Kanno, Takeshi Shimizu, Daichi Komabayashi, Kei Ito
Journal: Endoscopy (2024)

Endoscopic placement of a metal stent was attempted in an 80-year-old man with bowel obstruction due to cancer of the rectosigmoid colon ([Fig. 1]). Because of the severe angulation deformity of the tract, the lumen could not be identified using a standard scope (CF-HQ290ZI; Olympus, Tokyo, Japan). Therefore, we switched to an EG-840TP scope (Fujifilm, Tokyo, Japan) [1] ([Fig. 2]), a novel thin scope of outer diameter 7.9 mm for gastrointestinal therapeutic procedures. This scope has similar specifications to conventional therapeutic scopes, including an accessory channel with a diameter of 3.2 mm and an adequate down-angle function, making it useful for interventions in confined spaces. Using this scope, a guidewire was easily advanced into the oral side of the colonic obstruction with a secure frontal view of the intracancer lumen. Moreover, the scope could be advanced beyond the cancer stricture without resistance. A Hanarostent (Boston Scientific Japan K.K., Tokyo, Japan) was partially deployed at the proximal colon side with endoscopic imaging, and was then fully opened using a within-the-scope channel (intra-scope channel) stent release technique [2] ([Video 1], [Fig. 3]).
Successful endoscopic full-thickness resection and hand suturing for rectal subepithelial tumors
Authors: Naohiko Akimoto, Osamu Goto, Yumiko Ishikawa, Eriko Koizumi, Kazutoshi Higuchi, Jun Omori, Katsuhiko Iwakiri
Journal: Endoscopy (2024)

The efficacy of endoscopic full-thickness resection (EFTR) for a rectal subepithelial tumor is a known fact [1] [2] [3]; however, the provision of a secure closure still remains debatable. We report two successful cases of EFTR in which endoscopic hand suturing was employed to close a full-thickness defect.
Endoscopic ultrasound-guided drainage of bilomas in difficult-to-puncture locations using a sheath-assisted puncture technique
Authors: Kazuki Hama, Yukitoshi Matsunami, Takayoshi Tsuchiya, Reina Tanaka, Ryosuke Tonozuka, Shuntaro Mukai, Takao Itoi
Journal: Endoscopy (2024)

Biloma is a complication of transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) [1]. Despite being the first-line treatment for infected bilomas, percutaneous drainage can affect daily life and pose self-extraction risks, particularly in older patients [2]. Endoscopic ultrasound (EUS)-guided drainage offers a viable alternative for internal biliary drainage; however, it can be challenging for the right liver lobe because of its long distance from the gastrointestinal (GI) tract [3] [4] [5]. Here, we describe successful EUS-guided drainage of an infected biloma distant from the GI tract using a sheath-assisted puncture technique ([Fig. 1], [Video 1]).
An optional choice for closing the duodenal defect after endoscopic full-thickness resection: endoscopic hand-suturing
Authors: Yong Liu, Hoi-loi Ng, Shi-Bo Song, Shun He, Gui-Qi Wang
Journal: Endoscopy (2024)

A 51-year-old man went to hospital for routine examination and a 0-IIa lesion was found in the descending part of the duodenum, which the pathologic result showed to be a neuroendocrine tumor, Grade 1 ([Fig. 1] a). Endoscopic ultrasonography showed the lesion to be located in the muscularis mucosae and submucosal layer, and partly associated with the muscularis propria. After preoperative discussion and consent from the patient, our team decided to perform endoscopic full-thickness resection to remove the lesion ([Fig. 1] b). After resection, endoscopic hand-suturing was used to close the defect uneventfully ([Fig. 1] c, d, e, [Video 1]).
Endoscopic ultrasonography-guided single balloon-occluded gastrojejunostomy bypass: A case report
Authors: Ping-ping Zhang, Ting Yang, Kai-Xuan Wang, Yu Zhang
Journal: Endoscopy (2024)

A 67-year-old man presented at our institution with yellow staining of his skin and sclera for more than 1 month. Laboratory examination showed high concentrations of total bilirubin and carbohydrate antigen 19–9. Contrast-enhanced computed tomography (CT) of the abdomen showed pancreatic cancer with common bile duct and pancreatic duct stenosis. The horizontal part of the duodenum was invaded by the stenosis, obstructing the superior mesenteric artery and vein ([Fig. 1]). The findings of endoscopic ultrasound (EUS) were consistent with those of CT ([Fig. 2]), and gastro-enterography showed a narrowing of a 2.8-cm length of the duodenum ([Fig. 3]).
Endoscopy-assisted endotracheal intubation for advanced interventional procedures requiring general anesthesia
Authors: Jingjing Yao, Yongbin Han, Lei Kong, Wenwen Hou, Qiuzi Yang, Jindong Fu
Journal: Endoscopy (2024)

In complex upper gastrointestinal tract endoscopic submucosal dissection (ESD) procedures, prolonged operations increase the risk of bleeding and patient aspiration. To mitigate these risks and ensure patient safety, tracheal intubation is often required [1]. Here, we report an endoscopy-assisted tracheal intubation technique that enhances safety and efficiency ([Video 1]).
Hand-made mesh traction band to improve lateral view in colorectal endoscopic submucosal dissection
Authors: Tomoki Shimizu, Yusuke Takai, Eiji Sakai
Journal: Endoscopy (2024)

In endoscopic submucosal dissection of large colorectal lesions, use of single traction results in a poor lateral view owing to the weight of the lesion. Conventional traction devices are not elastic, and use of additional traction clips induces excessive traction force and specimen damage, limiting the size of the lesions that can be accommodated [1] [2] [3]. Moreover, using multiple traction devices increases costs, complicates device removal procedures, and is time consuming [4] [5]. No single device that allows multiple lateral tractions in any situation has been established. Therefore, we developed a novel device: the mesh traction band (MTB).
Standard peroral endoscopic myotomy combined with open peroral endoscopic myotomy for refractory sigmoid-type achalasia
Authors: Fu Guan, Boying Liu, Qunji Zhang, Shengbing Wang
Journal: Endoscopy (2024)

Peroral endoscopic myotomy (POEM) is a feasible, safe, and effective endoscopic treatment for achalasia [1] [2] [3]. However, standard POEM has limitations when managing sigmoid-type achalasia due to the complexity of anatomical structure in this type of achalasia [4]. We report a case of refractory sigmoid-type achalasia that was successfully treated with a combination of standard POEM and open POEM.
Staphylococcus epidermidis bacteremia after small bowel enteroscopy
Authors: Saif Ullah, Faisal Shaukat Ali, Xin-Guang Cao, Fangbin Zhang
Journal: Endoscopy (2024)

A 61-year-old man with a 6-month history of recurrent hematochezia was admitted to our hospital for the management of symptomatic anemia. Upon admission, his hemoglobin level was 60 g/L. Esophagogastroduodenoscopy and colonoscopy were performed but did not reveal the cause of his anemia. Subsequently, single-balloon enteroscopy (SBE) was conducted, which identified an actively bleeding angioectasia in the distal jejunum, approximately 300 cm from the incisors ([Fig. 1] a, [Video 1]). Hemostasis was achieved using argon plasma coagulation and hemoclip placement at the bleeding site ([Fig. 1] b, c). The SBE procedure time was approximately 13 min. Two days post-SBE, the patient developed a fever, peaking at 39°C, along with leukocytosis (white blood cell count: 21 × 109/L). A computed tomography (CT) scan of the chest and abdomen did not reveal any source of infection.
Endoscopic ultrasound-guided retrieval of a migrated plastic stent from a pelvic abscess
Authors: Koichi Soga, Yuto Suzuki, Fuki Hayakawa, Takeshi Fujiwara, Yo Fujimoto, Ikuhiro Kobori, Masaya Tamano
Journal: Endoscopy (2024)

Endoscopic ultrasound (EUS)-guided pelvic abscess drainage is a minimally invasive procedure; however, the anatomical challenges and restricted space can lead to complications [1]. This case report describes the migration of a plastic stent into a pelvic abscess cavity and its subsequent retrieval using a thin endoscope in a 55-year-old Japanese man with a pelvic abscess secondary to a hepatic abscess.
Potential hazards of gas generation during underwater endoscopic submucosal dissection
Authors: Tatsuma Nomura, Hiroaki Kumazawa, Yoshiaki Isono, Tomonori Saito, Ayman Qawasmi, Yoshikazu Hayashi, Katsumi Mukai
Journal: Endoscopy (2024)

It has been reported that endoscopic submucosal dissection (ESD) is performed under saline immersion for safer and more efficient resection [1] [2]. However, the generation of bubbles during submucosal dissection poses a significant challenge by obstructing the endoscopic view. Therefore, we developed a gas-free immersion system, an advanced method enabling ESD to be conducted without compromising the visual field [3] [4].
scCTS: identifying the cell type-specific marker genes from population-level single-cell RNA-seq
Authors: Luxiao Chen, Zhenxing Guo, Tao Deng, Hao Wu
Journal: Genome biology (2024)

Single-cell RNA-sequencing (scRNA-seq) provides gene expression profiles of individual cells from complex samples, facilitating the detection of cell type-specific marker genes. In scRNA-seq experiments with multiple donors, the population level variation brings an extra layer of complexity in cell type-specific gene detection, for example, they may not appear in all donors. Motivated by this observation, we develop a statistical model named scCTS to identify cell type-specific genes from population-level scRNA-seq data. Extensive data analyses demonstrate that the proposed method identifies more biologically meaningful cell type-specific genes compared to traditional methods.
Immune-related events in individuals with solid tumors on immunotherapy associate with Th17 and Th2 signatures
Authors: Chester J Kao, Soren Charmsaz, Stephanie L Alden, Madelena Brancati, Howard L Li, Aanika Balaji, Kabeer Munjal, Kathryn Howe, Sarah Mitchell, James Leatherman, Ervin Griffin, Mari Nakazawa, Hua-Ling Tsai, Ludmila Danilova, Chris Thoburn, Jennifer Gizzi, Nicole E Gross, Alexei Hernandez, Erin M Coyne, Sarah M Shin, Jayalaxmi Suresh Babu, George W Apostol, Jennifer Durham, Brian J Christmas, Maximilian F Konig, Evan J Lipson, Jarushka Naidoo, Laura C Cappelli, Aliyah Pabani, Yasser Ged, Marina Baretti, Julie Brahmer, Jean Hoffman-Censits, Tanguy Y Seiwert, Rachel Garonce-Hediger, Aditi Guha, Sanjay Bansal, Laura Tang, Elizabeth M Jaffee, G Scott Chandler, Rajat Mohindra, Won Jin Ho, Mark Yarchoan
Journal: Journal of Clinical Investigation (2024)

BACKGROUNDImmune-related adverse events (irAEs) and their associated morbidity/mortality are a key concern for patients receiving immune checkpoint inhibitors (ICIs). Prospective evaluation of the drivers of irAEs in a diverse pan-tumor cohort is needed to identify patients at greatest risk and to develop rational treatment and interception strategies.METHODSIn an observational study, we prospectively collected blood samples and performed regular clinical evaluations for irAEs in patients receiving ICI therapy as standard of care for solid tumors. We performed in-parallel analysis of cytokines by Luminex immunoassay and circulating immune cells by cytometry by time-of-flight (CyTOF) at baseline and on treatment to investigate mechanisms of irAEs.RESULTSWe enrolled 111 patients, of whom 40.5% developed a symptomatic irAE (grade ≥ 2). Development of a grade ≥ 2 irAE was positively associated with the use of combination ICI and a history of an autoimmune disorder. Early changes in T helper 17 (Th17) (IL-6, IL-17f), type 2 (IL-5, IL-13, IL-25), and type 1 (TNF-α) cytokine signatures and congruent on-treatment expansions of Th17 and Th2 effector memory (Th2EM) T cell populations in peripheral blood were positively associated with the development of grade ≥2 irAEs. IL-6 levels were also associated with inferior cancer-specific survival and overall survival.CONCLUSIONSIn a diverse, prospective pan-tumor cohort, Th17 and Th2 skewing during early ICI treatment was associated with the development of clinically relevant irAEs but not antitumor responses, providing possible targets for monitoring and therapeutic interventions.FUNDINGJohns Hopkins Bloomberg-Kimmel Institute for Cancer Immunotherapy, the NCI SPORE in Gastrointestinal Cancers (P50 CA062924), NCI grant (R50CA243627 to LD), the NIH Center Core Grant (P30 CA006973), Swim Across America (to MY), NIAMS (K23AR075872 to LC), and imCORE-Genentech grant 137515 (to Johns Hopkins Medicine on behalf of MY).
Trends in Oral and Injectable HIV Preexposure Prophylaxis Prescriptions in the US, 2013-2023
Authors: Laura M. Mann, Weiming Zhu, Ya-Lin A. Huang, Athena P. Kourtis, Robyn Neblett Fanfair, Karen W. Hoover
Journal: JAMA (2024)

This study examines the prescribing trends of 3 oral preexposure prophylaxis medications and a long-acting injectable option from 2013 to 2023.
Mpox Clinical Presentation, Diagnostic Approaches, and Treatment Strategies
Authors: Boghuma K. Titanji, Aniruddha Hazra, Jason Zucker
Journal: JAMA (2024)

Importance A global outbreak of clade IIb Monkeypox virus (MPXV) infections spread rapidly across at least 118 countries resulting in a Public Health Emergency of International Concern (PHEIC) from July 2022 to May 2023. This outbreak affected more than 99 000 persons worldwide and caused more than 33 000 infections and 60 deaths in the US. In 2024, there have been approximately 200 new infections per month in the US. On August 14, 2024, the World Health Organization declared mpox a PHEIC for a second time due to a rapid increase in infections with clade I MPXV in Central Africa. Observations Mpox is primarily acquired through direct skin to skin contact with MPXV. With clade IIb MPXV, infections are most commonly associated with sexual activity among individuals who are gay, bisexual, and other men who have sex with men. After a median incubation period of 7 to 10 days, prodromal symptoms include fever (62%-72%), lymphadenopathy (56%-86%), myalgias (31%-55%), malaise (23%-57%), and headache (25%-55%). Skin lesions progress through 4 well-defined stages (macules, papules, vesicles, and pustules) over 2 to 4 weeks. Clade IIb MPXV is typically a self-limited illness with a low mortality rate (&amp;amp;lt;0.2% in the US); however, severe illness and death may occur in immunocompromised individuals, especially those with advanced HIV (CD4 count &amp;amp;lt;200 cells/μL). Mpox should be suspected in patients with potential exposure to MPXV who have skin lesions, and the diagnosis is confirmed with polymerase chain reaction testing of lesions. Management is supportive and focuses on skin care and symptom relief with analgesics. While no antiviral treatments are currently approved for mpox by the US Food and Drug Administration, several therapeutics, such as tecovirimat, brincidofovir, and vaccinia immune globulin intravenous, are available through expanded access programs or clinical trials. Vaccination with the 2-dose Modified Vaccinia Ankara-Bavarian Nordic vaccine is recommended for high-incidence populations and has an efficacy of 66% to 86%. Conclusions and Relevance Mpox is a viral infection transmitted primarily through close skin to skin contact that typically causes a self-resolving illness but can result in severe illness and death in immunocompromised individuals. First-line therapy is supportive care, although patients with severe mpox infection may be treated with advanced therapeutics. Mpox vaccination is effective and, if available, should be offered to individuals at risk of exposure to mpox.
Best practice guide for patellofemoral pain based on synthesis of a systematic review, the patient voice and expert clinical reasoning
Authors: Bradley Stephen Neal, Simon David Lack, Clare Bartholomew, Dylan Morrissey
Journal: British Journal of Sports Medicine (2024)

Objective Define a best practice guide for managing people with patellofemoral pain (PFP). Methods A mixed-methods convergent segregated synthesis of meta-analysed data with a thematic analysis of semistructured interviews and focus groups. Agreement between subproject results informed the strength of clinical recommendation for interventions eligible for best practice recommendation. Data sources Medline, Web of Science, Scopus, reference lists and citation tracking; semistructured interviews of people with PFP; and semistructured interviews and focus groups with clinical experts. Eligibility criteria High-quality (PEDro scale &gt;7) randomised controlled trials (RCTs) were retained for efficacy estimation using meta-analysis. People with PFP were required to have experienced an episode of care in the past 6 months and clinical experts were required to have&gt;5 years of clinical experience alongside direct involvement in research. Results Data from 65 high-quality RCTs involving 3796 participants informed 11 meta-analyses of interventions. Interviews with 12 people with PFP led to 3 themes and interviews with 19 clinical experts led to 4 themes. These were further explored in three clinical expert focus groups. Best practice for PFP should first involve understanding a patient’s background risk factors, their reasons for seeking care, greatest symptoms, and physical impairments, to inform treatment selection. Synthesis led to six distinct interventions being recommended. Knee-targeted±hip-targeted exercise therapy underpinned by education should be delivered, with additional supporting interventions such as prefabricated foot orthoses, manual therapy, movement/running retraining, or taping decided on and tailored to a patient’s needs and preferences. Conclusion A best practice guide based on a synthesis of three data streams recommends that exercise therapy and education be delivered as the primary intervention for people with PFP. Prescription of other supporting interventions should be aligned with the individual patient’s particular presentation following a thorough assessment.
Circadian Clock Disruption and Growth of Kidney Cysts in Autosomal Dominant Polycystic Kidney Disease
Authors: Abeda Jamadar, Christopher J. Ward, Viji Remadevi, Meekha M. Varghese, Navjot S. Pabla, Michelle L. Gumz, Reena Rao
Journal: Journal of the American Society of Nephrology (2024)

Key Points Lack of Bmal1 , a circadian clock protein in renal collecting ducts disrupted the clock and increased cyst growth and fibrosis in an autosomal dominant polycystic kidney disease mouse model. Bmal1 gene deletion increased cell proliferation by increasing lipogenesis in kidney cells. Thus, circadian clock disruption could be a risk factor for accelerated disease progression in patients with autosomal dominant polycystic kidney disease. Background Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in the PKD1 and PKD2 genes and often progresses to kidney failure. ADPKD progression is not uniform among patients, suggesting that factors secondary to the PKD1/2 gene mutation could regulate the rate of disease progression. Here, we tested the effect of circadian clock disruption on ADPKD progression. Circadian rhythms are regulated by cell-autonomous circadian clocks composed of clock proteins. BMAL1 is a core constituent of the circadian clock. Methods To disrupt the circadian clock, we deleted Bmal1 gene in the renal collecting ducts of the Pkd1 RC/RC (RC/RC) mouse model of ADPKD (RC/RC; Bmal1 f/f ; Pkhd1 cre , called double knockout [DKO] mice) and in Pkd1 knockout mouse inner medullary collecting duct cells ( Pkd1Bmal1 KO mouse renal inner medullary collecting duct cells). Only male mice were used. Results Human nephrectomy ADPKD kidneys showed altered clock gene expression when compared with normal control human kidneys. When compared with RC/RC kidneys, DKO kidneys showed significantly altered clock gene expression, increased cyst growth, cell proliferation, apoptosis, and fibrosis. DKO kidneys also showed increased lipogenesis and cholesterol synthesis–related gene expression and increased tissue triglyceride levels compared with RC/RC kidneys. Similarly, in vitro , Pkd1Bmal1 KO cells showed altered clock genes, increased lipogenesis and cholesterol synthesis–related genes, and reduced fatty acid oxidation–related gene expression compared with Pkd1KO cells. The Pkd1Bmal1 KO cells showed increased cell proliferation compared with Pkd1KO cells, which was rescued by pharmacological inhibition of lipogenesis. Conclusions Renal collecting duct–specific Bmal1 gene deletion disrupted the circadian clock and triggered accelerated ADPKD progression by altering lipid metabolism–related gene expression.
A soccer-based intervention improves incarcerated individuals’ behaviour and public acceptance through group bonding
Authors: Martha Newson, Linus Peitz, Jack Cunliffe, Harvey Whitehouse
Journal: Nature Human Behaviour (2024)

As incarceration rates rise globally, the need to reduce re-offending grows increasingly urgent. We investigate whether positive group bonds can improve behaviours among incarcerated people via a unique soccer-based prison intervention, the Twinning Project. We analyse effects of participation compared to a control group (study 1, n = 676, n = 1,874 control cases) and longitudinal patterns of social cohesion underlying these effects (study 2, n = 388) in the United Kingdom. We also explore desistance from crime after release (study 3, n = 249) in the United Kingdom and the United States. As law-abiding behaviour also requires a supportive receiving community, we assessed factors influencing willingness to employ formerly incarcerated people in online samples in the United Kingdom and the United States (studies 4-9, n = 1,797). Results indicate that social bonding relates to both improved behaviour within prison and increased willingness of receiving communities to support re-integration efforts. Harnessing the power of group identities both within prison and receiving communities can help to address the global incarceration crisis.