Genomic profiling of post-transplant lymphoproliferative disorders using cell-free DNA

Diagnosing post-transplant lymphoproliferative disorder (PTLD) is challenging and often requires invasive procedures. Analyses of cell-free DNA (cfDNA) isolated from plasma is minimally invasive and highly effective for genomic profiling of tumors. We studied the feasibility of using cfDNA to profile PTLD and explore its potential to serve as a screening tool. We included seventeen patients with monomorphic PTLD after solid organ transplantation in this multi-center observational cohort study. We used low-coverage whole genome sequencing (lcWGS) to detect copy number variations (CNVs) and targeted next-generation sequencing (NGS) to identify Epstein-Barr virus (EBV) DNA load and somatic single nucleotide variants (SNVs) in cfDNA from plasma. Seven out of seventeen (41%) patients had EBV-positive tumors, and 13/17 (76%) had stage IV disease. Nine out of seventeen (56%) patients showed CNVs in cfDNA, with more CNVs in EBV-negative cases. Recurrent gains were detected for 3q, 11q, and 18q. Recurrent losses were observed at 6q. The fraction of EBV reads in cfDNA from EBV-positive patients was 3-log higher compared to controls and EBV-negative patients. 289 SNVs were identified, with a median of 19 per sample. SNV burden correlated significantly with lactate dehydrogenase levels. Similar SNV burdens were observed in EBV-negative and EBV-positive PTLD. The most commonly mutated genes were TP53 and KMT2D (41%), followed by SPEN, TET2 (35%), and ARID1A, IGLL5, and PIM1 (29%), indicating DNA damage response, epigenetic regulation, and B-cell signaling/NFkB pathways as drivers of PTLD. Overall, CNVs were more prevalent in EBV-negative lymphoma, while no difference was observed in the number of SNVs. Our data indicated the potential of analyzing cfDNA as a tool for PTLD screening and response monitoring.</p

Genomic profiling of post-transplant lymphoproliferative disorders using cell-free DNA

Diagnosing post-transplant lymphoproliferative disorder (PTLD) is challenging and often requires invasive procedures. Analyses of cell-free DNA (cfDNA) isolated from plasma is minimally invasive and highly effective for genomic profiling of tumors. We studied the feasibility of using cfDNA to profile PTLD and explore its potential to serve as a screening tool. We included seventeen patients with monomorphic PTLD after solid organ transplantation in this multi-center observational cohort study. We used low-coverage whole genome sequencing (lcWGS) to detect copy number variations (CNVs) and targeted next-generation sequencing (NGS) to identify Epstein-Barr virus (EBV) DNA load and somatic single nucleotide variants (SNVs) in cfDNA from plasma. Seven out of seventeen (41%) patients had EBV-positive tumors, and 13/17 (76%) had stage IV disease. Nine out of seventeen (56%) patients showed CNVs in cfDNA, with more CNVs in EBV-negative cases. Recurrent gains were detected for 3q, 11q, and 18q. Recurrent losses were observed at 6q. The fraction of EBV reads in cfDNA from EBV-positive patients was 3-log higher compared to controls and EBV-negative patients. 289 SNVs were identified, with a median of 19 per sample. SNV burden correlated significantly with lactate dehydrogenase levels. Similar SNV burdens were observed in EBV-negative and EBV-positive PTLD. The most commonly mutated genes were TP53 and KMT2D (41%), followed by SPEN, TET2 (35%), and ARID1A, IGLL5, and PIM1 (29%), indicating DNA damage response, epigenetic regulation, and B-cell signaling/NFkB pathways as drivers of PTLD. Overall, CNVs were more prevalent in EBV-negative lymphoma, while no difference was observed in the number of SNVs. Our data indicated the potential of analyzing cfDNA as a tool for PTLD screening and response monitoring

Evaluation of National Surgical Practice for Lateral Lymph Nodes in Rectal Cancer in an Untrained Setting

Background: Involved lateral lymph nodes (LLNs) have been associated with increased local recurrence (LR) and ipsi-lateral LR (LLR) rates. However, consensus regarding the indication and type of surgical treatment for suspicious LLNs is lacking. This study evaluated the surgical treatment of LLNs in an untrained setting at a national level. Methods: Patients who underwent additional LLN surgery were selected from a national cross-sectional cohort study regarding patients undergoing rectal cancer surgery in 69 Dutch hospitals in 2016. LLN surgery consisted of either ‘node-picking’ (the removal of an individual LLN) or ‘partial regional node dissection’ (PRND; an incomplete resection of the LLN area). For all patients with primarily enlarged (≥7 mm) LLNs, those undergoing rectal surgery with an additional LLN procedure were compared to those undergoing only rectal resection. Results: Out of 3057 patients, 64 underwent additional LLN surgery, with 4-year LR and LLR rates of 26% and 15%, respectively. Forty-eight patients (75%) had enlarged LLNs, with corresponding recurrence rates of 26% and 19%, respectively. Node-picking (n = 40) resulted in a 20% 4-year LLR, and a 14% LLR after PRND (n = 8; p = 0.677). Multivariable analysis of 158 patients with enlarged LLNs undergoing additional LLN surgery (n = 48) or rectal resection alone (n = 110) showed no significant association of LLN surgery with 4-year LR or LLR, but suggested higher recurrence risks after LLN surgery (LR: hazard ratio [HR] 1.5, 95% confidence interval [CI] 0.7–3.2, p = 0.264; LLR: HR 1.9, 95% CI 0.2–2.5, p = 0.874). Conclusion: Evaluation of Dutch practice in 2016 revealed that approximately one-third of patients with primarily enlarged LLNs underwent surgical treatment, mostly consisting of node-picking. Recurrence rates were not significantly affected by LLN surgery, but did suggest worse outcomes. Outcomes of LLN surgery after adequate training requires further research.</p

Gender differences in respiratory symptoms in 19-year-old adults born preterm

Objective: To study the prevalence of respiratory and atopic symptoms in (young) adults born prematurely, differences between those who did and did not develop Bronchopulmonary Disease (BPD) at neonatal age and differences in respiratory health between males and females. Methods: Design: Prospective cohort study. Setting: Nation wide follow-up study, the Netherlands. Participants: 690 adults (19 year old) born with a gestational age below 32 completed weeks and/or with a birth weight less than 1500g. Controls were Dutch participants of the European Community Respiratory Health Survey (ECRHS). Main outcome measures: Presence of wheeze, shortness of breath, asthma, hay fever and eczema using the ECRHS-questionnaire

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

The genus Premna (Lamiaceae) and the presence of \u27pyro-herbs\u27 in the Flora Malesiana area

Volume: 63Start Page: 495End Page: 49

Machilus coriacea A. Chev. 2023, sp. nov.

13. Machilus coriacea A.Chev. ex de Kok, sp. nov. (Figs 12; 14) Machilus coriacea A.Chev. unpublished; P.H.Hô, Câycỏ Việtnam 1: 489 (Hô 1991), nom. inval.; Nguyén Kim &Dstrok;ào, Lauraceae in Checklist of Plant Species of Vietnam 2: 101 (Nguyén Kim &Dstrok;ào 2003), nom. inval.; Nguyén Kim &Dstrok;ào, Flora of Vietnam 20: 95 (Nguyén Kim &Dstrok;ào 2017), nom. inval. DIAGNOSIS. — This species differs from its close relative Machilus grandibracteata S.K.Lee & F.N.Wei, which has twigs that are glabrous and leaves with 9-11 pairs of secondary nerves (while M. coriacea A.Chev. ex de Kok, sp. nov. has sparsely hairy twigs and leaves with 7-9 pairs of secondary nerves); inflorescence which are densely hairy and perianth lobes which are sparsely hairy inside and outside (while M. coriacea A.Chev. ex de Kok, sp. nov. has inflorescence which are sparsely hairy and perianth lobes densely hairy inside and outside). TYPE SPECIMEN. — [Vietnam] Bien Hoa: Dinh Quan, 11°9’24.66”N, 107°15’8.928”E, 4.XII.1932, Poilane 21630 (holo-, P [P02004544]; iso-, E[no barcode]). VERNACULAR NAME. — Vietnamese: Kháo dai (Nguyén Kim &Dstrok;ào 2017: 95). DISTRIBUTION. — Vietnam (see Fig. 12). ECOLOGY. — Growing in forest, sometimes over limestone, between 1000-1500 m altitude. Flowering from Nov. to January; fruiting in Sept. CONSERVATION. — Endangered B2ab(i,ii,iii,iv) This species is only known from five collections from Vietnam. An analysis of the Extent of Occurrence (EOO) and Area of Occupancy (AOO) gives an IUCN Conservation Assessment of Endangered. ADDITIONAL COLLECTIONS SEEN. — Vietnam. Nha Trang: Massif du Hon-Ba, 12°22’59.988”N, 108°52’59.988”E, alt. c. 1000-1500 m, 1.IX.1918, Chevalier 38881 (P00476642, P02004595, P02004596, P02004597); Lang Son: Bang Mac, 17.I.1941, Pételot 6729 (P); Vinh: Tam Dao, 21°20’7.008”N, 105°35’21.012”E, IV.1931, Pételot 4680 (P02008991); Saigon: Hoc-Môn, 10°53’16.008”N, 106°35’39.012”E, XI.1942, Anonymous 9197 (P02003810). DESCRIPTION Trees 10-20 m tall, dbh 20-25 cm. Twigs slender, 1.6-3 mm thick, rounded in cross-section, sparsely hairy; hairs appressed, yellowish; terminal leaf bud ovoid 5-7 mm long, apex acute, velutinous, imbricate. Leaves alternate; blade elliptic to oblanceolate, 6-16 × 2.5-7.6 cm, apex acute, base cuneate, leathery, penninerved, secondary nerves 7-9 pairs, curved towards margin, tertiary nerves scalariform-reticular; upper surface glabrous, midrib and secondary nerves sunken, tertiary nerves indistinct; lower surface sparsely hairy, midrib and secondary nerves raised, tertiary nerves distinct; hairs yellowish, erect; petiole channelled, 18-20 mm long, sparsely hairy, slender. Inflorescence 10-15 cm long, terminal, sparsely hairy; bracts leaf-like; bracteoles linear, c. 2 mm long. Flowers white; perianth lobes 2.4-4.5 × 1.1-1.4 mm, apex acute, densely hairy inside and outside; stamens 9, 3.4-4 mm long, glabrous; ovary c. 0.7 mm diam. Fruit globular, 18-20 × 16-18 mm, apex rounded, glabrous; perianth lobes 7.5-8 × 2.9-3.6 mm, apex acute, densely hairy, erect, patent to reflexed, membranous (see Fig. 14).Published as part of De Kok, Rogier P. J., 2023, The Lauraceae Juss. of Indo-China: fifteen new species, four new combinations and two neotypifications, pp. 1-25 in Adansonia (3) (3) 45 (1) on pages 18-20, DOI: 10.5252/adansonia2023v45a1, http://zenodo.org/record/752247

Actinodaphne sesquipedalis subsp. cambodiana de Kok 2023

3. Actinodaphne sesquipedalis Hook.f. & Thoms. ex Meisn. subsp. cambodiana (Lecomte) de Kok, comb. nov, stat. nov. Actinodaphne sesquipedalis var. cambodiana Lecomte, Archives du Muséum d’Histoire naturelle, Paris, sér. V., 5: 93 (Lecomte 1913). — Type: Cambodia. Krepeuh, Monts Knang, 14°18’9”N, 103°50’40.992”E, alt. 1500 m, IX.1870, J.B.L. Pierre 627 (lecto-, P [P02035687], first step lectotypification by Tanaros et al., Thai Journal of Botany 2: 17 (Tanaros et al. 2010), second step lectotypification here; isolecto-, A[A00041110, A00936321], B[B 10 0241815], BM[BM000951003], E[E00386461], F[F0061313F], K[K000350900], NY[NY00354780], P[P01062897, P01880075, P02008331, P02008332, P02008333, P02035673, P02035677, P02035678, P02035683, P02035684, P02035686, P02035688, P02035705, P02194623, P06837464]). REMARKS This taxon is much better recognised on subspecies level as it has a distinct separated distribution, relative to the other subspecies of this species in Thailand and Penninsular Malaysia.Published as part of De Kok, Rogier P. J., 2023, The Lauraceae Juss. of Indo-China: fifteen new species, four new combinations and two neotypifications, pp. 1-25 in Adansonia (3) (3) 45 (1) on page 22, DOI: 10.5252/adansonia2023v45a1, http://zenodo.org/record/752247