Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib: primary results from the phase III MARIPOSA-2 study.

BACKGROUND: Amivantamab plus carboplatin-pemetrexed (chemotherapy) with and without lazertinib demonstrated antitumor activity in patients with refractory epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer (NSCLC) in phase I studies. These combinations were evaluated in a global phase III trial. PATIENTS AND METHODS: A total of 657 patients with EGFR-mutated (exon 19 deletions or L858R) locally advanced or metastatic NSCLC after disease progression on osimertinib were randomized 2 : 2 : 1 to receive amivantamab-lazertinib-chemotherapy, chemotherapy, or amivantamab-chemotherapy. The dual primary endpoints were progression-free survival (PFS) of amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy. During the study, hematologic toxicities observed in the amivantamab-lazertinib-chemotherapy arm necessitated a regimen change to start lazertinib after carboplatin completion. RESULTS: All baseline characteristics were well balanced across the three arms, including by history of brain metastases and prior brain radiation. PFS was significantly longer for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy [hazard ratio (HR) for disease progression or death 0.48 and 0.44, respectively; P < 0.001 for both; median of 6.3 and 8.3 versus 4.2 months, respectively]. Consistent PFS results were seen by investigator assessment (HR for disease progression or death 0.41 and 0.38 for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy, respectively; P < 0.001 for both; median of 8.2 and 8.3 versus 4.2 months, respectively). Objective response rate was significantly higher for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy (64% and 63% versus 36%, respectively; P < 0.001 for both). Median intracranial PFS was 12.5 and 12.8 versus 8.3 months for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy (HR for intracranial disease progression or death 0.55 and 0.58, respectively). Predominant adverse events (AEs) in the amivantamab-containing regimens were hematologic, EGFR-, and MET-related toxicities. Amivantamab-chemotherapy had lower rates of hematologic AEs than amivantamab-lazertinib-chemotherapy. CONCLUSIONS: Amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy improved PFS and intracranial PFS versus chemotherapy in a population with limited options after disease progression on osimertinib. Longer follow-up is needed for the modified amivantamab-lazertinib-chemotherapy regimen.

Fluorescent-Nanoparticle-Impregnated Nanocomposite Polymeric Gels for Biosensing and Drug Delivery Applications.

Nanocomposite polymeric gels infused with fluorescent nanoparticles have surfaced as a propitious category of substances for biomedical purposes owing to their exceptional characteristics. The aforementioned materials possess a blend of desirable characteristics, including biocompatibility, biodegradability, drug encapsulation, controlled release capabilities, and optical properties that are conducive to imaging and tracking. This paper presents a comprehensive analysis of the synthesis and characterization of fluorescent-nanoparticle-impregnated nanocomposite polymeric gels, as well as their biomedical applications, such as drug delivery, imaging, and tissue engineering. In this discourse, we deliberate upon the merits and obstacles linked to these substances, encompassing biocompatibility, drug encapsulation, optical characteristics, and scalability. The present study aims to provide an overall evaluation of the potential of fluorescent-nanoparticle-impregnated nanocomposite polymeric gels for biomedical applications. Additionally, emerging trends and future directions for research in this area are highlighted.

Synthesis of Transition-Metal-Doped Nanocatalysts with Antibacterial Capabilities Using a Complementary Green Method.

A facile single-step wet chemical synthesis of a transition-metal-doped molybdate derivative was achieved via an Ocimum tenuiflorum extract-mediated green approach. The Synthesized nanomaterials of doped molybdate were characterized by optical and other spectroscopic techniques, which confirmed the size of nanocrystalline (~27.3 nm). The thermal stability of the nanomaterials confirmed through thermogravimetric analysis showed similarity with nanomaterials of Mn-ZnMoO4. Moreover, the nanoparticles displayed a non-toxic nature and showed antibactericidal activity. The impact of doping was reflected in band gap measurements; undoped ZnMoO4 showed relatively lower band gap in comparison to Mn-doped ZnMoO4. In the presence of light, ZnMoO4 nanomaterials a exhibited photocatalytic response to solochrome dark blue dye with a concentration of 50 ppm. OH- and O2*- radicals also destroyed the blue color of the dye within 2 min and showed potential antibactericidal activity towards both Gram-positive and Gram-negative bacteria, representing a unique application of the green-synthesized nanocatalyst.

Doped Carbon Quantum Dots Reinforced Hydrogels for Sustained Delivery of Molecular Cargo.

Hydrogels have emerged as important soft materials with numerous applications in fields including biomedicine, biomimetic smart materials, and electrochemistry. Because of their outstanding photo-physical properties and prolonged colloidal stability, the serendipitous findings of carbon quantum dots (CQDs) have introduced a new topic of investigation for materials scientists. CQDs confined polymeric hydrogel nanocomposites have emerged as novel materials with integrated properties of the individual constituents, resulting in vital uses in the realm of soft nanomaterials. Immobilizing CQDs within hydrogels has been shown to be a smart tactic for preventing the aggregation-caused quenching effect and also for manipulating the characteristics of hydrogels and introducing new properties. The combination of these two very different types of materials results in not only structural diversity but also significant improvements in many property aspects, leading to novel multifunctional materials. This review covers the synthesis of doped CQDs, different fabrication techniques for nanostructured materials made of CQDs and polymers, as well as their applications in sustained drug delivery. Finally, a brief overview of the present market and future perspectives are discussed.

Inter-morph pollen flow and reproductive success in a self-compatible species with stigma-height dimorphism: the influence of herkogamy and reciprocity.

Inter-morph pollen transfer and its dependence on herkogamy and reciprocity are not completely understood in species with stigma-height dimorphism. We asked whether total stigmatic pollen loads, inter-morph fraction of pollen load and reproductive success differed between morphs in Jasminum malabaricum, a species exhibiting stigma-height dimorphism. We tested whether higher herkogamy and reciprocity resulted in higher inter-morph pollen deposition and reproductive success. We quantified individual-level estimates of herkogamy, reciprocity, total stigmatic pollen load, inter-morph stigmatic pollen fraction and fruit set for both morphs in naturally occurring populations of J. malabaricum. Total pollen load was higher in the long-styled morph, inter-morph pollen fraction was higher in the short-styled morph, but fruit set did not differ between morphs. Higher herkogamy resulted in a higher inter-morph fraction of pollen load and fruit set in the long-styled morph of one population. In the other population, only reciprocity was found to be related to inter-morph pollen deposition. This study is the first to quantify and report natural inter-morph stigmatic pollen load in a species with stigma-height dimorphism. Morph-specific differences in pollen load were similar to patterns commonly observed in heterostylous species. The results highlight the importance of both herkogamy and reciprocity in facilitating inter-morph pollen transfer. Population-specific patterns indicate that local environmental factors determine the relative functional importance of herkogamy and reciprocity.

Precision therapy with anaplastic lymphoma kinase inhibitor ceritinib in ALK-rearranged anaplastic large cell lymphoma.

BACKGROUND: More than 80% of anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) patients harbor the (nucleophosmin) NPM1-ALK fusion gene t(2;5) chromosomal translocation. We evaluated the preclinical and clinical efficacy of ceritinib treatment of this aggressive lymphoma. MATERIALS AND METHODS: We studied the effects of ceritinib treatment in NPM1-ALK+ T-cell lymphoma cell lines in vitro and on tumor size and survival advantage in vivo utilizing tumor xenografts. We treated an NPM1-ALK+ ALCL patient with ceritinib. We reviewed all hematologic malignancies profiled by a large hybrid-capture next-generation sequencing (NGS)-based comprehensive genomic profiling assay for ALK alterations. RESULTS: In our in vitro experiments, ceritinib inhibited constitutive activation of the fusion kinase NPM1-ALK and downstream effector molecules STAT3, AKT, and ERK1/2, and induced apoptosis of these lymphoma cell lines. Cell cycle analysis following ceritinib treatment showed G0/G1 arrest with a concomitant decrease in the percentage of cells in S and G2/M phases. Further, treatment with ceritinib in the NPM1-ALK+ ALCL xenograft model resulted in tumor regression and improved survival. Of 19 272 patients with hematopoietic diseases sequenced, 58 patients (0.30%) harbored ALK fusions that include histiocytic disorders, multiple myeloma, B-cell neoplasms, Castleman's disease, and juvenile xanthogranuloma. A multiple relapsed NPM1-ALK+ ALCL patient treated with ceritinib achieved complete remission with ongoing clinical benefit to date, 5 years after initiation of therapy. CONCLUSIONS: This ceritinib translational study in NPM1-ALK+ ALCL provides a strong rationale for a prospective study of ceritinib in ALK+ T-cell lymphomas and other ALK+ hematologic malignancies.

Aberrant CREB1 activation in prostate cancer disrupts normal prostate luminal cell differentiation.

The molecular mechanisms of luminal cell differentiation are not understood well enough to determine how differentiation goes awry during oncogenesis. Using RNA-Seq analysis, we discovered that CREB1 plays a central role in maintaining new luminal cell survival and that oncogenesis dramatically changes the CREB1-induced transcriptome. CREB1 is active in luminal cells, but not basal cells. We identified ING4 and its E3 ligase, JFK, as CREB1 transcriptional targets in luminal cells. During luminal cell differentiation, transient induction of ING4 expression is followed by a peak in CREB1 activity, while JFK increases concomitantly with CREB1 activation. Transient expression of ING4 is required for luminal cell induction; however, failure to properly down-regulate ING4 leads to luminal cell death. Consequently, blocking CREB1 increased ING4 expression, suppressed JFK, and led to luminal cell death. Thus, CREB1 is responsible for the suppression of ING4 required for luminal cell survival and maintenance. Oncogenic transformation by suppressing PTEN resulted in constitutive activation of CREB1. However, the tumor cells could no longer fully differentiate into luminal cells, failed to express ING4, and displayed a unique CREB1 transcriptome. Blocking CREB1 in tumorigenic cells suppressed tumor growth in vivo, rescued ING4 expression, and restored luminal cell formation, but ultimately induced luminal cell death. IHC of primary prostate tumors demonstrated a strong correlation between loss of ING4 and loss of PTEN. This is the first study to define a molecular mechanism whereby oncogenic loss of PTEN, leading to aberrant CREB1 activation, suppresses ING4 expression causing disruption of luminal cell differentiation.

Pre-Transplant Marital Status and Hematopoietic Cell Transplantation Outcomes

Background: Evidence about the impact of marital status before hematopoietic cell transplantation (hct) on outcomes after hct is conflicting. Methods: We identified patients 40 years of age and older within the Center for International Blood and Marrow Transplant Research registry who underwent hct between January 2008 and December 2015. Marital status before hct was declared as one of: married or living with a partner, single (never married), separated or divorced, and widowed. We performed a multivariable analysis to determine the association of marital status with outcomes after hct. Results: We identified 10,226 allogeneic and 5714 autologous hct cases with, respectively, a median follow-up of 37 months (range: 1-102 months) and 40 months (range: 1-106 months). No association between marital status and overall survival was observed in either the allogeneic (p = 0.58) or autologous (p = 0.17) setting. However, marital status was associated with grades 2-4 acute graft-versus-host disease (gvhd), p < 0.001, and chronic gvhd, p = 0.04. The risk of grades 2-4 acute gvhd was increased in separated compared with married patients [hazard ratio (hr): 1.13; 95% confidence interval (ci): 1.03 to 1.24], and single patients had a reduced risk of grades 2-4 acute gvhd (hr: 0.87; 95% ci: 0.77 to 0.98). The risk of chronic gvhd was lower in widowed compared with married patients (hr: 0.82; 95% ci: 0.67 to 0.99). Conclusions: Overall survival after hct is not influenced by marital status, but associations were evident between marital status and grades 2-4 acute and chronic gvhd. To better appreciate the effects of marital status and social support, future research should consider using validated scales to measure social support and patient and caregiver reports of caregiver commitment, and to assess health-related quality of life together with health care utilization.

Leptin and obesity.

An imbalance between calorie intake and energy expenditure produces obesity. It has been a major problem in societies of the developing and developed world. In obesity an excessive amount of fat accumulates in adipose tissue cells as well as in other vital organs like liver, muscles, and pancreas. The adipocytes contain ob genes and express leptin, a 16 kDa protein. In the present communication, we reviewed the molecular basis of the etiopathophysiology of leptin in obesity. Special emphasis has been given to the use of leptin as a drug target for obesity treatment, the role of diet in the modulation of leptin secretion, and reduction of obesity at diminished level of blood leptin induced by physical exercise.

High herkogamy but low reciprocity characterizes isoplethic populations of Jasminum malabaricum, a species with stigma-height dimorphism.

Studies of floral polymorphisms have focused on heterostyly, while stigma-height dimorphism has received considerably less attention. Few studies have examined the reproductive biology of species with stigma-height dimorphism to understand how factors influencing mate availability and pollen transfer are related to morph ratios in populations. Floral morphological traits, especially herkogamy and reciprocity, pollinator visitation, breeding system and spatiotemporal mate availability, are known to affect inter-morph pollination and morph ratios in species with stigma-height dimorphism. In this study, we investigated the presence of stigma-height dimorphism and estimated morph ratios in four naturally occurring populations of Jasminum malabaricum. We quantified morph- and population-specific differences in the abovementioned factors in these populations to understand the observed morph ratios. The positions of anthers and stigmas were characteristic of stigma-height dimorphism, the first report of this polymorphism in the genus. All study populations were isoplethic, implying equal fitness of both morphs. Herkogamy was higher in the short-styled morph, while reciprocity was higher between the long-styled stigma and short-styled anthers. Long- and short-tongued pollinators were common floral visitors, and we observed no differences between morphs in spatiotemporal mate availability or pollinator visitation. Neither morph exhibited self- or heteromorphic incompatibility. The short-styled stigma had lower reciprocity but likely receives sufficient inter-morph pollen from long-tongued pollinators, and also by avoiding self-pollination due to higher herkogamy. These results highlight the importance of sufficient effective pollinators and floral morphological features, particularly herkogamy, in maintaining isoplethy in species with stigma-height dimorphism.

Determination of size dependent carrier capture in InGaN/GaN quantum nanowires by femto-second transient absorption spectroscopy: effect of optical phonon, electron-electron scattering and diffusion.

Understanding the ultrafast processes corresponding to carrier capture, thermalization and relaxation is essential to design high speed optoelectronic devices. Here, we have investigated a size dependent carrier capture process in InGaN/GaN 20, 50 nm nanowires and quantum well systems. Femto-second transient absorption spectroscopy reveals that the carrier capture is a two-step process. The carriers are captured in the barrier by polar optical phonon (POP) scattering. They further scatter into the active region by electron-electron and POP scatterings. The capture is found to slow down for quantum confined structures. A significant number of carriers are found to disappear from the barrier during the diffusion process. All the experimental observations are explained in a simulation framework depicting various scattering mechanisms.

Weight loss associated with sodium-glucose cotransporter-2 inhibition: a review of evidence and underlying mechanisms.

With their novel, insulin-independent mechanism, sodium-glucose cotransporter-2 (SGLT2) inhibitors are a major turning point in the management of type 2 diabetes mellitus. At present, there are several SGLT2 inhibitors available or in development, and these oral anti-hyperglycaemic agents lower plasma glucose through the inhibition of SGLT2-mediated reuptake of filtered glucose in the kidney. This unique mechanism of action is also expected to result in other beneficial effects, such as weight loss and blood pressure reduction. In various studies, including randomized controlled trials and real-world studies, patients treated with SGLT2 inhibitors have reported weight loss of around 1 to 3 kg. This review describes the characteristics of weight loss associated with SGLT2 inhibitor therapy, the clinical factors affecting SGLT2 inhibitor-associated weight loss and the possible underlying mechanisms of SGLT2 inhibitor-associated weight loss, including changes in metabolism and body composition, and the role of a reduction in insulin dose and compensatory hyperphagia. Understanding the weight loss effect of SGLT2 inhibitors, its related factors and underlying mechanisms can aid clinicians in optimal treatment decision-making, provide valuable insight on both obesity and diabetes management and reveal areas of future research and new therapeutic options.

The effect of India's total sanitation campaign on defecation behaviors and child health in rural Madhya Pradesh: a cluster randomized controlled trial

Poor sanitation is thought to be a major cause of enteric infections among young children. However, there are no previously published randomized trials to measure the health impacts of large-scale sanitation programs. India's Total Sanitation Campaign (TSC) is one such program that seeks to end the practice of open defecation by changing social norms and behaviors, and providing technical support and financial subsidies. The objective of this study was to measure the effect of the TSC implemented with capacity building support from the World Bank's Water and Sanitation Program in Madhya Pradesh on availability of individual household latrines (IHLs), defecation behaviors, and child health (diarrhea, highly credible gastrointestinal illness [HCGI], parasitic infections, anemia, growth).

Strong Size Dependency on the Carrier and Photon Dynamics in InGaN/GaN Single Nanowalls Determined Using Photoluminescence and Ultrafast Transient Absorption Spectroscopy.

Here, we have demonstrated strong size dependency of quasi-equilibrium and nonequilibrium carrier and photon dynamics in InGaN/GaN single nanowalls using photoluminescence and transient absorption spectroscopy. We demonstrate that two-dimensional carrier confinement, strain relaxation, and modified density of states lead to a reduced Stokes shift, smaller full width at half-maxima, increased exciton binding energy, and reduced nonradiative recombination. The ultrafast transient spectroscopy shows that carrier capture is a two-step process dominated by optical phonons and carrier-carrier scattering in succession. The carrier capture is a strongly size-dependent process and becomes slower due to modulation of the density of available states for progressively decreasing nanowall sizes. The slowest process is the electron-hole recombination, which is also extremely size-dependent and the rate increases by almost an order of magnitude in comparison to that of quantum-well structures. Electron-hole wave function overlap and modified density of states are among the key aspects in determining all the properties of these structures.

The myeloid immune signature of enterotoxigenic Bacteroides fragilis-induced murine colon tumorigenesis.

Enterotoxigenic Bacteroides fragilis (ETBF), a human commensal and candidate pathogen in colorectal cancer (CRC), is a potent initiator of interleukin-17 (IL-17)-dependent colon tumorigenesis in MinApc+/- mice. We examined the role of IL-17 and ETBF on the differentiation of myeloid cells into myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages, which are known to promote tumorigenesis. The myeloid compartment associated with ETBF-induced colon tumorigenesis in Min mice was defined using flow cytometry and gene expression profiling. Cell-sorted immature myeloid cells were functionally assayed for inhibition of T-cell proliferation and inducible nitric oxide synthase expression to delineate MDSC populations. A comparison of ETBF infection with that of other oncogenic bacteria (Fusobacterium nucleatum or pks+Escherichia coli) revealed a specific, ETBF-associated colonic immune infiltrate. ETBF-triggered colon tumorigenesis is associated with an IL-17-driven myeloid signature characterized by subversion of steady-state myelopoiesis in favor of the generation of protumoral monocytic-MDSCs (MO-MDSCs). Combined action of the B. fragilis enterotoxin BFT and IL-17 on colonic epithelial cells promoted the differentiation of MO-MDSCs, which selectively upregulated Arg1 and Nos2, produced NO, and suppressed T-cell proliferation. Evidence of a pathogenic inflammatory signature in humans colonized with ETBF may allow for the identification of populations at risk for developing colon cancer.

Association of ABO blood group polymorphism and tuberculosis: A study on Bengalee Hindu caste population, West Bengal, India.

Tuberculosis (TB) is an infectious disease commonly caused by the bacillus mycobacterium and worldwide estimation demonstrated that more than 8.6 million people are infected by TB. Many of the previous studies reported the association between TB and ABO blood group polymorphism. In this context, the objective of the present study is to understand the association of ABO blood group polymorphism and TB in Bengalee Hindu caste population. The present study consists of 100 clinically diagnosed TB patients and 100 apparently healthy individuals with no previous history of TB from the same population of the same area. The distribution of ABO phenotypes demonstrated significant (p<0.05) excess of AB blood group in TB patients and significant (p<0.05) decrease of O blood group in controls. Logistic regression analysis revealed that individuals with non O blood group have 1.97 times (95% CI 1.04-3.75) greater chance of developing TB than individuals with O blood group.

Association of p53 codon72 Arg>Pro polymorphism with susceptibility to nasopharyngeal carcinoma: evidence from a case-control study and meta-analysis.

Tumor suppressor p53 is a critical player in the fight against cancer as it controls the cell cycle check point, apoptotic pathways and genomic stability. It is known to be the most frequently mutated gene in a wide variety of human cancers. Single-nucleotide polymorphism of p53 at codon72 leading to substitution of proline (Pro) in place of arginine (Arg) has been identified as a risk factor for development of many cancers, including nasopharyngeal carcinoma (NPC). However, the association of this polymorphism with NPC across the published literature has shown conflicting results. We aimed to conduct a case-control study for a possible relation of p53 codon72 Arg>Pro polymorphism with NPC risk in underdeveloped states of India, combine the result with previously available records from different databases and perform a meta-analysis to draw a more definitive conclusion. A total of 70 NPC patients and 70 healthy controls were enrolled from different hospitals of north-eastern India. The p53 codon72 Arg>Pro polymorphism was typed by polymerase chain reaction, which showed an association with NPC risk. In the meta-analysis consisting of 1842 cases and 2330 controls, it was found that individuals carrying the Pro allele and the ProPro genotype were at a significantly higher risk for NPC as compared with those with the Arg allele and the ArgArg genotype, respectively. Individuals with a ProPro genotype and a combined Pro genotype (ProPro+ArgPro) also showed a significantly higher risk for NPC over a wild homozygote ArgArg genotype. Additionally, the strength of each study was tested by power analysis and genotype distribution by Hardy-Weinberg equilibrium. The outcome of the study indicated that both allele frequency and genotype distribution of p53 codon72 Arg>Pro polymorphism were significantly associated with NPC risk. Stratified analyses based on ethnicity and source of samples supported the above result.

The combination of FLT3 and DNA methyltransferase inhibition is synergistically cytotoxic to FLT3/ITD acute myeloid leukemia cells.

Effective treatment regimens for elderly acute myeloid leukemia (AML) patients harboring internal tandem duplication mutations in the FMS-like tyrosine kinase-3 (FLT3) gene (FLT3/ITD) are lacking and represent a significant unmet need. Recent data on the effects of FLT3 tyrosine kinase inhibitors on FLT3/ITD(+) AML showed promising clinical activity, including in elderly patients. DNA methyltransferase (DNMT) inhibitors such as decitabine (5-aza-2-deoxycytidine, DEC) and 5-azacitidine (AZA) demonstrated clinical benefit in AML, are well tolerated and are associated with minimal increases in FLT3 ligand, which can represent a potential resistance mechanism to FLT3 inhibitors. In addition, both FLT3 and DNMT inhibition are associated with the induction of terminal differentiation of myeloid blasts. Consequently, there is a strong theoretical rationale for combining FLT3 and DNMT inhibition for FLT3/ITD(+) AML. We therefore sought to study the anti-leukemic effects of DEC, AZA and FLT3 inhibitors, either as single agents or in combination, on AML cell lines and primary cells derived from newly diagnosed and relapsed AML patients. Our studies indicate that combined treatment using FLT3 inhibition and hypomethylation confers synergistic anti-leukemic effects, including apoptosis, growth inhibition and differentiation. The simultaneous administration of AZA and FLT3 inhibition appears to be the most efficacious combination in this regard. These drugs may provide a novel therapeutic approach for FLT3/ITD(+) AML, in particular for older patients.

Observation of B

We report the first observation of the decays B^{0}→pΛ[over ¯]D^{(*)-}. The data sample of 711 fb^{-1} used in this analysis corresponds to 772×10^{6} BB[over ¯] pairs, collected at the ϒ(4S) resonance by the Belle detector at the KEKB asymmetric-energy e^{+}e^{-} collider. We observe 19.8σ and 10.8σ excesses of events for the two decay modes and measure the branching fractions of B^{0}→pΛ[over ¯]D^{-} and B^{0}→pΛ[over ¯]D^{*-} to be (25.1±2.6±3.5)×10^{-6} and (33.6±6.3±4.4)×10^{-6}, respectively, where the first uncertainties are statistical and the second are systematic. These results are not compatible with the predictions based on the generalized factorization approach. In addition, a threshold enhancement in the dibaryon (pΛ[over ¯]) system is observed, consistent with that observed in similar B decays.